Search NASA⌕ Search

SEARCH · Search NASA

Results for “PROLIFERATION”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes

Background: In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats. Methods: MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC. IGF1 was also downregulated by siRNA in miR-29-downregulated GK MMEVC. Its effect on miR-29-associated angiogenic regulation on MMEVC proliferation and migration was further investigated. Results: MiR-29 was substantially upregulated in GK MMEVC than in Wistar MMEVC. Transfection of synthetic miR-29 inhibitor successfully downregulate endogenous miR-29 in GK MMEVC, and subsequently promoted angiogenesis by increasing cell proliferation and migration. IGF1 was confirmed to be downstream target gene of miR-29 in GK MMEVC, with its gene and protein expressions both upregulated in miR-29-downregualted GK MMEVC. Conversely, siRNA-mediated IGF1 downregulation reversed the pro-angiogenic effect of miR-29 downregulation in GK MMEVC, as it decreased cell proliferation and migration. Conclusion: Our study suggests that miR-29 downregulation, through its inverse regulation on downstream target of IGF1 gene, is a pro-angiogenic factor in MMEVC in type 2 diabetic rats.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Circular RNA hsa-circ-0010729 regulates vascular endothelial cell proliferation and apoptosis by targeting the miR-186/HIF-1α axis

Circular RNAs (circRNAs) are a group of non-protein-coding RNAs generated from back splicing. Emerging evidence has demonstrated its vital regulation on angiogenesis. However, the underlying mechanism responsible for circRNAs effects on vascular endothelial cells is still unclear. In the present study, we screened the expression profiles and investigated the physiological role of circRNAs in hypoxia-induced human umbilical vein endothelial cells (HUVECs). Using circRNA microarray analysis, we identified 36 circRNAs that were significantly dysregulated including 14 down-regulated circRNAs and 22 up-regulated with 2-fold change (P < 0.05). From the over-expressed circRNAs, hsa-circ-0010729 was selected as candidate circRNA and which was validated to be significantly up-regulated using RT-PCR. In loss-of-function experiments of HUVECs, hsa-circ-0010729 knockdown suppressed the proliferation and migration ability and enhanced apoptosis. Bioinformatic prediction and luciferase assay revealed that hsa-circ-0010729 and hypoxia inducible factor 1 alpha (HIF-1α) were targeted by miR-186. Validation experiments verified that hsa-circ-0010729 was co-expressed with HIF-1α, being negatively correlated with miR-186. Moreover, rescue experiments demonstrated that miR-186 inhibitor could reverse the role of hsa-circ-0010729 knockdown on HUVECs progression. Overall, the present study identifies the crucial regulation of hsa-circ-0010729 on vascular endothelial cell proliferation and apoptosis via targeting miR-186/HIF-1α axis. - Highlights: • Circular RNA expression profile identifies hsa-circ-0010729 is up-regulated in hypoxia-induced HUVECs. • Hsa-circ-0010729 knockdown suppresses the proliferation and migration ability, and enhanced the apoptosis. • Hsa-circ-0010729 acts as an endogenous sponge of miR-186. • HIF-1α is targeted by miR-186. • Hsa-circ-0010729 regulates vascular endothelial cells proliferation and apoptosis via targeting miR-186/HIF-1α axis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Aloe-emodin (AE) nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo

Human lung squamous cell carcinoma is a deadly cancer for which present therapeutic strategies are inadequate. And traditional chemotherapy results in severe systemic toxicity. Compounds from living organisms often exert a biological activity, triggering several targets, which may be useful for the improvement of novel pharmaceuticals. Aloe-emodin (AE), a well-known natural compound, is a primary component of anthraquinones in Aloe vera and exhibits anti-proliferative and apoptotic effects on various tumor cells. However, the translational and clinical use of AE has been limited owing to its rapid degradation and poor bioavailability. To improve its efficacy, a poly (lactic-co-glycolic acid) based AE nanoparticle formulation (NanoAE) was prepared. Our study indicated that compared to the free AE, nanoAE significantly suppressed cancer cell proliferation, induced cell cycle arrest and apoptosis, evidenced by high cleavage of Caspase-3, poly (ADP-ribose) polymerase (PARP), Caspase-8 and Caspase-9. NanoAE enhanced reactive oxygen species (ROS) production, along with Mitogen-activated protein kinases (MAPKs) activation and PI3K/AKT inactivation. Cell proliferation, apoptosis and MAPKs and PI3K/AKT were dependent on ROS production in nanoAE-treated groups. In vivo, nanoAE exhibited inhibitory effects on the tumor growth with little toxicity. Together, our results indicated that nanoAE might be an effective treatment for human lung squamous cell carcinoma. - Highlights: • Aloe-emodin nanoparticles (NanoAE) displayed significant anti-tumor effect in lung squamous carcinoma. • NanoAE inhibited cell proliferation and induced apoptosis in squamous carcinoma cells. • NanoAE up-regulated ROS levels in apoptosis and cell proliferation process. • NanoAE suppresses the growth of human squamous carcinoma mice in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Upregulated long non-coding RNA LOC90784 promotes cell proliferation and invasion and is associated with poor clinical features in HCC

A growing amount of literature has indicated that long non-coding RNAs (lncRNAs) are important factors in hepatocellular carcinoma (HCC) progression. However, the significance of lncRNAs in the progression and prognosis of liver cancer is largely unknown. In the present study, upregulated lncRNA LOC90784 was identified through integrative analysis of (GSE58043) and (GSE55191). Furthermore, associations between LOC90784 expression and the clinicopathological characteristics of patients were analyzed with a validated cohort 1 and the Cancer Genome Atlas (TCGA) cohort 2. We investigated the mechanisms by which this highly expressed lncRNA promotes HCC proliferation, invasion and migration via qRT-PCR, fluorescence in situ hybridization (FISH) staining, siRNA transfection, cell proliferation assays, Transwell and colony formation assays, flow cytometry analysis and Western blot. The results showed that LOC90784 expression levels were significantly higher in HCC cell lines and tissues and mainly localized in the cytoplasm. Knockdown of lncRNA LOC90784 expression inhibited proliferation and induced apoptosis and cell cycle arrest by promoting Bax and repressing CDK4 and Cyclin D1 protein expression; it also inhibited invasion and migration by repressing MMP2 and MMP9 expression in HCC cells. LOC90784 overexpression was associated with poor clinical features in the two cohorts and poor overall survival rates in HCC patients with clear resection margins (R0) in cohort 2. These results indicated that LOC90784 upregulation may be a critical oncogene and potential new biomarker in HCC. - Highlights: • LncRNA LOC90784 was overexpressed in HCC tissues and cell lines. • Highly expressed lncRNA LOC90784 was associated with poor clinical features in HCC. • Knockdown of lncRNA LOC90784 expression inhibited proliferation and induced apoptosis and cell cycle arrest. • Knockdown of lncRNA LOC90784 expression inhibited invasion and migration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Irisin stimulates cell proliferation and invasion by targeting the PI3K/AKT pathway in human hepatocellular carcinoma

Irisin is a newly identified myokine that may be cancer-associated, and its impact on liver cancer is unclear. To understand the roles of irisin in liver cancer, we investigated its effect in HepG2 and SMCC7721 hepatocellular carcinoma cells, and the underlying mechanisms. We determined irisin levels in liver tissues and serum samples obtained from patients by using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Irisin levels in cancerous livers were significantly upregulated compared with those in control livers, but serum irisin levels remained unchanged. Additionally, we evaluated the effects of different concentrations of human recombinant modified and active (glycosylated) irisin (IM) or human recombinant nonmodified irisin (INM) on cell migration, proliferation, viability, and invasiveness. CCK8, transwell, and scratching assays demonstrated that irisin significantly increased cell proliferation, invasion, and migration through activation of the PI3K/AKT pathway. Irisin-induced cell proliferation, migration, and invasion were blocked by a PI3K inhibitor (LY294002). Irisin also decreased the cytotoxicity of doxorubicin in HepG2 cells. These data indicate that increased irisin levels may have protective roles in liver cancer cells through partial activation of the PI3K/AKT pathway, which may facilitate liver cancer progression and decrease the sensitivity to chemotherapy. - Highlights: • Irisin levels are upgraded in patients with hepatocellular carcinoma. • Irisin induces cell proliferation, migration, invasiveness, and inhibit appotosis of cell induced by Dox. • Irisin induces the activation of PI3K/AKT pathway. • Irisin has protective roles in liver cancer cells, inducing disease progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

MiR-362-3p inhibits the proliferation and migration of vascular smooth muscle cells in atherosclerosis by targeting ADAMTS1

Atherosclerosis is a progressive condition of the large arteries that can cause coronary artery disease (CAD). Growing amounts of evidence have indicated that microRNAs (miRNAs, miRs) can be used as diagnostic biomarkers in many cellular processes associated with CAD. MiR-362-3p has been implicated in many biological cellular functions. However, little is known about the role of miR-362-3p during atherosclerosis. In the present study, significant downregulation of miR-362-3p was observed in 110 atherosclerotic CAD patients and not in the 84 controls. The upregulation of miR-362-3p was demonstrated to inhibit vascular smooth muscle cell (VSMC) proliferation and migration, and impede the G1/S cell cycle transition. Bioinformatics analysis indicated that a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) was a direct target of miR-362-3p. Subsequent experiments demonstrated that miR-362-3p binds to the 3′-untranslated region (UTR) of ADAMTS1 and decreases its levels of mRNA and protein expression. Overexpression of ADAMTS1 partially restored the miR-362-3p-mediated inhibition of VSMC proliferation, cell cycle, and migration. Upregulation of ADAMTS1 in plasma samples was detected in atherosclerotic CAD patients. Taken together, our findings suggested that miR-362-3p inhibits the proliferation and migration of VSMCs by directly targeting ADAMTS1, which might provide novel insight into the molecular mechanisms underlying the action of miR-362-3p in atherosclerosis. - Highlights: • MiR-362-3p expression is downregulated in the plasma samples of atherosclerotic CAD patients. • MiR-362-3p overexpression inhibits VSMC proliferation, cell cycle progression, and migration. • ADAMTS1 is a direct target of miR-362-3p. • Dysfunction of miR-362-3p may contribute to the pathophysiology of atherosclerosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer

Highlights: • LncRNA-PVT1-5 is up-regulated in lung cancer tissues and cell lines. • LncRNA-PVT1-5 acted as a sponge for miR-126 to regulate cells proliferation in lung cancer cells. • LncRNA-PVT1-5 exerts its role via miR-126/SLC7A5 axis in lung cancer cell modes. Dysregulated long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. The lncRNA plasmacytoma variant translocation 1 (PVT1) is reported to be an oncogene in a variety of cancers. However, the roles of PVT1-5 and its related miRNAs in lung cancer are poorly understood. In this study, we found that PVT1-5 expression was significantly increased in lung cancer tissues and cell lines. By using biotin-labeled lncRNA-PVT1-5 probe for miRNA in vivo precipitation (miRIP) in lung cancer cells and dual-luciferase reporterassays, we identified that miR-126 was associated with lncRNA-PVT1-5. Furthermore, knockdown of lncRNA-PVT1-5 in cells could down-regulate the expression of SLC7A5, the target of oncogenic miR-126, resulting in the cell proliferation. Conversely, inhibiting the expression of miR-126 markedly increased the expression of SLC7A5 and alleviated cell proliferation inhibition. Thus, our results indicated that lncRNA-PVT1-5 may function as a competing endogenous RNA (ceRNA) for miR-126 to promote cell proliferation by regulating the miR-126/SLC7A5 pathway, suggesting that lncRNA-PVT1-5 plays a crucial role in lung cancer progression and lncRNA-PVT1-5/miR-126/SLC7A5 regulatory network may shed light on tumorigenesis in lung cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA circMAN2B2 facilitates lung cancer cell proliferation and invasion via miR-1275/FOXK1 axis

Highlights: • CircMAN2B2 knockdown suppresses lung cancer cell proliferation and invasion. • CircMAN2B2 sponges and represses miR-1275 expression in lung cancer. • miR-1275 exerts its role by regulation of FOXK1 expression in lung cancer. • CircMAN2B2 promotes lung cancer cell proliferation an invasion via circMAN2B2/miR-1275/FOXK1 signaling. Lung cancer remains a leading cause of cancer-related deaths worldwide. In the past years, increasing reports indicate that circular RNAs (circRNAs) exert a great important role in human cancers, including lung cancer. However, the knowledge about circRNA in lung cancer remains very little so far. In the present study, we screened out a highly expressed novel circRNA named circMAN2B2 in lung cancer tissues. We investigated the function of circMAN2B2 and found that circMAN2B2 knockdown significantly inhibited cell proliferation and invasion in both H1299 and A549 lung cancer cells. Mechanistically, we found that circMAN2B2 could sponge miR-1275 to inhibit its level. Through a series of functional experiments, we dissected the role of miR-1275 in lung cancer and proved the anti-tumor role of miR-1275. Furthermore, we found that miR-1275 exerted its role in lung cancer by regulating FOXK1 expression. In addition, we demonstrated that restoration of FOXK1 could rescue circMAN2B2 knockdown-induced repression of cell proliferation and invasion. Taken together, our study demonstrated that circMAN2B2 acts as an oncogenic role in lung cancer through promoting FOXK1 expression by sponging miR-1275.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Tyrosine kinase activity of EphA2 promotes its S897 phosphorylation and glioblastoma cell proliferation

Highlights: • Overexpression of EphA2 induces its S897 phosphorylation without growth factor stimulation. • Tyrosine kinase of EphA2 promotes EphA2-induced S897 phosphorylation. • Overexpression of EphA2 induces ERK activation through its tyrosine kinase activity. • ERK activation is required for EphA2-induced S897 phosphorylation. • Tyrosine kinase of EphA2 promotes glioblastoma cell proliferation. EphA2, a member of the Eph family of receptor tyrosine kinases, has been reported to promote tumor malignancy through phosphorylation of serine 897 (S897). Here, we found that overexpression of wild-type EphA2 induced S897 phosphorylation through ERK activation without growth factors or cytokines and promoted glioblastoma cell proliferation. However, overexpression of a kinase-inactive mutant of EphA2 failed to induce ERK activation, S897 phosphorylation, and promotion of glioblastoma cell proliferation. These data suggest that when overexpressed, EphA2 induces ERK activation through its tyrosine kinase activity, leading to S897 phosphorylation and promotion of glioblastoma cell proliferation. Our findings provide a new insight into how EphA2 mediates glioblastoma progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

FOXM1 promotes proliferation in human hepatocellular carcinoma cells by transcriptional activation of CCNB1

Highlights: • FOXM1 and CCNB1 are prognostic indicators in human hepatocellular carcinoma. • FOXM1 transcriptionally upregulates CCNB1 expression levels in HCC cells. • CCNB1 is essential for proliferation in HCC cells. • FOXM1 modulates HCC cell proliferation by targeting CCNB1. The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Spindle pole body component 25 homolog expressed by ECM stiffening is required for lung cancer cell proliferation

Highlights: • Matrix stiffness regulates the expression of genes involved in cell proliferation. • SPC25 is identified as hazard gene induced by matrix stiffness. • SPC25 is involved in cancer cell proliferation under stiff matrix conditions. • Depletion of SPC25 induces G2/M arrest via chromosome misalignment in metaphase. Accumulating evidence has shown that matrix stiffening in cancer tissue by the deposition of extracellular matrix (ECM) is closely related with severe tumor progression. However, much less is known about the genes affected by matrix stiffness and its signaling for cancer progression. In the current research, we investigated the differential gene expression of a non-small lung adenocarcinoma cell line, H1299, cultured under the conditions of soft (∼0.5 kPa) and stiff (∼40 kPa) matrices, mimicking the mechanical environments of normal and cancerous tissues, respectively. For integrated transcriptome analysis, the genes identified by ECM stiffening were compared with 8248 genes retrieved from The Cancer Genome Atlas Lung Adenocarcinoma (TCGA). In stiff matrix, 29 genes were significantly upregulated, while 75 genes were downregulated. The screening of hazard ratios for these genes using the Kaplan-Meier Plotter identified 8 genes most closely associated with cancer progression under the condition of matrix stiffening. Among these genes, spindle pole body component 25 homolog (SPC25) was one of the most up-regulated genes in stiff matrix and tumor tissue. Knockdown of SPC25 in H1299 cells using shRNA significantly inhibited cell proliferation with downregulation of the expression of checkpoint protein, Cyclin B1, under the condition of stiff matrix whereas the proliferation rate in soft matrix was not affected by SPC25 silencing. Thus, our findings provide novel key molecules for studying the relationship of extracellular matrix stiffening and cancer progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Down-regulation of LHPP in cervical cancer influences cell proliferation, metastasis and apoptosis by modulating AKT

Cervical cancer is a leading severe malignancy throughout the world. Though various pathologies associated with cervical cancer progression have been demonstrated, further study is still necessary to reveal the tumorigenesis of cervical cancer. The protein histidine phosphatase LHPP is reported as a tumor suppressor. Histidine phosphorylation, also known as hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. LHPP is evolutionarily conserved from worm to human. In the present study, we discovered that LHPP expression levels were lower in human cervical cancer tumors than that in adjacent normal tissue samples. LHPP expression levels were also reduced in several cervical cancer cell lines. Further, LHPP over-expression reduced the cell proliferation, migration and invasion, associated with the change of p53 and metastasis signaling pathways. Moreover, over-expressing LHPP markedly induced apoptosis in human cervical cancer cells via promoting the cleaved Caspse-3 and PARP. Importantly, we found that LHPP over-expression blocked AKT activation. Elevating AKT activity could abolish the role of LHPP over-expression in reducing cell proliferation and metastasis, as well as in inducing apoptotic response. Moreover, suppressing p53 expression with its inhibitor of PFTα abrogated the activity of LHPP to impede cell proliferation and metastasis, and to trigger apoptosis. AKT phosphorylation also restrained p53 expression levels in cervical cancer cells. In vivo, the anti-cervical cancer effects of LJPP were verified, which were also via the repression of cell proliferation and metastasis, and the induction of apoptosis. Therefore, LHPP could be considered as an effective candidate to develop effective therapeutic strategy against cervical cancer development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Reverse the down regulation of miR-92b-3p by hypoxia can suppress the proliferation of pulmonary artery smooth muscle cells by targeting USP28

Highlights: • miR-92b-3p reverse the proliferaton of pulmonary artery smooth muscle cells under hypoxia condition. • miR-92b-3p regulate the protein level of USP28. • miR-92b-3p maybe a novel treatment target of pulmonary hypertension. MiR-92b-3p has been shown to take part in several disease by regulate proliferation, apoptosis, differentiation and metastasis. However, the role of miR-92b-3p in pulmonary arterial hypertension (PAH) has not been illustrated clearly. Here, we found the level of miR-92b-3p which mainly located in the smooth muscle layer was down-regulation under hypoxic condition. It can inhibit pulmonary artery smooth muscle cells (PASMCs) proliferation and cell cycle progression. Through luciferase assay, miR-92b-3p bound to the 3′-UTR of USP28. we found that there was a significant negative relation between the level of miR-92b-3p and USP28 at protein level and reversed the down regulation of miR-92b-3p by hypoxia can suppress the proliferation of pulmonary artery smooth muscle cells by targeting USP28. These results suggested that miR-92b-3p acted a potential proliferation regulator in PASMCs and it maybe a novel treatment target of PAH.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LINC01510 suppresses cell proliferation and invasion by inhibiting Wnt/β-catenin signaling in renal cell carcinoma

Highlights: • LINC01510 is down-regulated in renal cell carcinoma (RCC) and predicts poor prognosis. • LINC01510 inhibits RCC cell proliferation and growth by affecting cell cycle transition from G0/G1 to S stage. • LINC01510 inhibits the expression of MMP2, MMP7 and MMP9, and then decrease the ability of RCC cell invasion. • LINC01510 regulates cell proliferation and invasion through Wnt/β-catenin signaling. The role of long non-coding RNA in Renal cell carcinoma (RCC) tumorigenesis and progression remains largely unknown. Here, we found that LINC01510 functions as a tumor suppressor in RCC tumorigenesis. We screened TCGA database and then found that LINC01510 is significantly down-regulated in malignant RCC tissues, and the lower expression of LINC01510 predicts poor prognosis. Moreover, the down-regulated LINC01510 was further confirmed in our fresh tissues and cell lines. Biological functions assays shown that Ectopic expression of LINC01510 not only inhibits RCC cell proliferation both in vitro and in vivo, but also impairs cell invasion ability. Moreover, we found overexpression of LINC01510 inhibits the expression of CCND1 and CCNE1, as well as MMPs (MMP2, MMP7 and MMP9), and thus affecting RCC cell cycle and invasion. Meanwhile, Western blot assays revealed that the expression of β-catenin is regulated by LINC01510; overexpression of β-catenin could partly rescue the cell viability and invasion ability caused by ectopic expression of LINC01510. Taken together, we found that LINC01510 regulates cell proliferation and invasion by modulating Wnt/β-catenin signaling in RCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Upregulation of 24(R/S),25-epoxycholesterol and 27-hydroxycholesterol suppresses the proliferation and migration of gastric cancer cells

Highlights: • Detection of oxysterols in human gastric tumour tissues and gastric juice. • 24(R/S),25-EC and 27HC were increased in human gastric tumour tissues. • Proliferation of gastric cancer cells were suppressed by 24(R/S),25-EC/27HC. • Migration of gastric cancer cells were suppressed by 24(R/S),25-EC/27HC. • Roles of LXRs in the regulation of proliferation/migration by 24(R/S),25-EC/27HC. Gastric cancer (GC) is one of the most common cancers and is the second-leading cause of cancer-associated morbidity worldwide. Oxysterols are oxidized derivatives of cholesterol that may be important in many biological processes, but the levels and roles of oxysterols in gastric tumours remain to be elucidated. The levels of cholesterol, oxysterols and sulfated oxysterols in human gastric tumour tissues, adjacent normal mucosal tissues, cancerous gastric juice and gastric juice obtained from healthy subjects were detected by LC-MS. It was found that the levels of 24(R/S),25-EC and 27HC in human gastric tumour tissues and cancerous gastric juice were significantly increased compared with those of adjacent normal mucosal tissues and gastric juice from healthy subjects. Compared with normal gastric mucosal tissue, the levels of sulfated 25-hydroxycholesterol (25HC3S) and the ratio of 25HC3S/25HC were decreased in human gastric tumour tissues, which might be related to the dramatically decreased SULT2A1 expression in gastric tumour tissue. Both 24(R/S),25-EC and 27HC suppressed gastric cancer proliferation, which was not altered by LXRα-siRNA treatment. The suppression of cell proliferation induced by 27HC was attenuated by LXRβ-siRNA, but the suppression of cell proliferation induced by 24(R/S),25-EC was intensified by LXRβ-siRNA. Both 24(R/S),25-EC and 27HC dramatically inhibited HGC-27 cell migration, which was attenuated by the co-transfection of cells with LXRα-siRNA and LXRβ-siRNA, but not LXRα-siRNA or LXRβ-siRNA alone. In conclusion, the accumulated 24(R/S),25-EC and 27HC in human gastric tumour tissues might play important roles in gastric cancer development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long noncoding RNA LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1

Highlights: • LOXL1-AS1 regulates proliferation and cell cycle in prostate cancer cells. • miR-541-3p regulates CCND1 expression in prostate cancer cells. • LOXL1-AS1 sponges and regulates the expression of miR-541-3p. • LOXL1-AS1 regulates proliferation and cell cycle through miR-541-3p and CCND1. Prostate cancer is one of the most frequent malignancies affecting men. Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer. LncRNA LOXL1-AS1 participates in the pathogenesis of the exfoliation syndrome. However, the role of LOXL1-AS1 in cancer remains largely unknown. Here, we found that LOXL1-AS1 down-regulation inhibited prostate cancer cell proliferation and cell cycle progression. RNA sequencing analysis revealed that it regulates the expression of cell cycle-related genes. LOXL1-AS1 is predominantly distributed in the cytoplasm, where it interacts with miR-541-3p. In addition, miR-541-3p targets the cell cycle regulator CCND1 in prostate cancer cells. LOXL1-AS1 down-regulation inhibits the expression of CCND1 and cell cycle progression, whereas these effects are abolished upon miR-541-3p suppression. In summary, our study revealed that LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1. Modulation of their levels may be used to treat prostate cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

SOX10-dependent CMTM7 expression inhibits cell proliferation and tumor growth in gastric carcinoma

Highlights: • The expression pattern of CMTM7 and SOX10 are down-regulated in GC. • SOX10 is a transcriptional regulator of CMTM7 in GC. • SOX10 mediate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7. Numerous studies have shown that CMTM family members have a variety of important roles in the occurrence and progression of cancer. CMTM7 has also been reported to be down-regulated in some digestive system tumors, but the expression patterns and pathological role of CMTM7 in gastric cancer remains unclear. In this study, we found that both CMTM7 and SOX10 were significantly down-regulated in gastric cancer tissues compared with paracancerous tissues, and the expression pattern of CMTM7 and SOX10 were strongly correlated (r = 0.6455, p < 0.001). Further, through bioinformatics technology and luciferase assay, we identify that SOX10 can be a transcriptional regulator of CMTM7 to mediate the expression of CMTM7 in gastric cancer. In addition, we found silencing the expression of CMTM7 can increase the proliferation and tumorigenesis of gastric cancer cells in vivo and in vitro. More interestingly, overexpression of SOX10 in cell lines stably silencing CMTM7 expression significantly inhibited the proliferation and tumor growth of gastric cancer. Therefore, our results demonstrate that CMTM7 as a tumor suppressor is down-regulated in gastric cancer, and SOX10 can regulate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in acute myeloid leukemia cells via sponging miR-203

Highlights: • Circular RNA-100290 expression is increased in AML patients. • Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in AML cells. • Circular RNA-100290 interacts with miR-203/Rab10 axis. Circular RNA (CirRNA) is a type of noncoding RNA that has been shown to play a unique role in tumor development and other fields in recent years. In this study, we aimed to explore the biological role of hsa{sub c}irc{sub 1}00290 in acute myeloid leukemia (AML). First, we found that the expression of hsa{sub c}irc{sub 1}00290 was increased in human AML samples and cell lines. Down-regulation of hsa{sub c}irc{sub 1}00290 significantly suppressed cell proliferation of AML cells. Silencing hsa{sub c}irc{sub 1}00290 also dramatically induced cell cycle arrest and apoptosis. Bioinformatic prediction and luciferase assay revealed that hsa{sub c}irc{sub 1}00290 and Rab10 were targeted by miR-203. Validation experiments verified that hsa{sub c}irc{sub 1}00290 was co-expressed with Rab10 and was negatively correlated with miR-203 expression. Moreover, rescue experiments demonstrated that miR-203 inhibitor could reverse the role of hsa{sub c}irc{sub 1}00290 knockdown on proliferation and apoptosis in AML cells. Overall, the present study identifies the crucial regulation of hsa{sub c}irc{sub 1}00290 in AML cell proliferation and apoptosis via targeting the miR-203/Rab10 axis.

60 APPLIED LIFE SCIENCES↗