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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.

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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Spatially Resolved Top-Down Proteomics of Tissue Sections Based on a Microfluidic Nanodroplet Sample Preparation Platform

Conventional proteomics measures the averaged signal from mixed cell populations or bulk tissues, leading to the dilution of significant changes in subpopulations of cells that might serve as important biomarkers. Recent developments in bottom-up proteomics have enabled spatial mapping of cellular heterogeneity in tissue microenvironments. However, bottom-up proteomics cannot precisely infer the abundance changes of intact proteins, which are presented as proteoforms. Herein, we described a spatially resolved top-down proteomics (TDP) platform for proteoform identification and quantification directly on thin tissue sections. The spatial TDP platform consisted of a nanoPOTS (nanodroplet Processing in One pot for Trace Samples)-based sample preparation system and an LCM (laser capture microdissection)-based cell isolation system. We improved the nanoPOTS sample preparation by adding benzonase in the extraction buffer to enhance the coverage of nucleus proteins. Using ~200 cultured cells as model samples, the improved approach increased proteoform identifications from 493 to 700; newly identified proteoforms primarily corresponded to nuclear proteins. To demonstrate the spatial TDP platform in tissue samples, we analyzed LCM-isolated tissue voxels from rat brain cortex and hypothalamus regions. We quantified 426 proteoforms by combining identifications from TopPIC and TDPortal with the quantitation from ProMex. Several proteoforms corresponding to the same gene exhibited mixed abundance profiles between two tissue regions, suggesting potential PTM-specific spatial distributions. The spatial TDP workflow has prospects for biomarker discovery at proteoform level from small tissue sections.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements

Type 1 diabetes (T1D) is a devastating autoimmune disease for which advanced mass spectrometry (MS) methods are increasingly used to identify new biomarkers and better understand underlying mechanisms. For example, integration of MS analysis and machine learning has identified multimolecular biomarker panels. In mechanistic studies, MS has contributed to the discovery of neoepitopes, and pathways involved in disease development and identifying therapeutic targets. However, challenges remain in understanding the role of tissue microenvironments, spatial heterogeneity, and environmental factors in disease pathogenesis. Recent advancements in MS, such as ultra-fast ion-mobility separations, and single-cell and spatial omics, can play a central role in addressing these challenges. Here, in this work, we review recent advancements in MS-based molecular measurements and their role in understanding T1D.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

An activatable NIR fluorescent rosol for selectively imaging nitroreductase activity

Hypoxia (i.e., pO 2 ≤ ~1.5 %) is an important characteristic of tumor microenvironments that directly correlates with resistance against first-line therapies and tumor proliferation/infiltration. The ability to accurately identify hypoxic tumor cells/tissue could afford tailored therapeutic regimens for personalized treatment, the development of more-effective therapies, and discerning the mechanisms underlying disease progression. Fluorogenic constructs currently developed for identifying such tumor cells/tissue operate by targeting the bioreductive activity of primarily the nitroreductase (NTR) class of enzymes, but collectively such constructs unfortunately present photophysical and/or physicochemical shortcomings that could limit their effectiveness upon implementation. To overcome these limitations, we present the rational design, development, and evaluation of the first activatable ultracompact xanthene core-based molecular probe (NO 2 -Rosol) for selectively imaging NTR activity that affords an “OFF-ON” near-infrared (NIR) fluorescence response (ca. > 700 nm) alongside a remarkable Stokes shift (ca. > 150 nm) via NTR activity-facilitated modulation to its energetics whereby the resultant interplay discontinues an intramolecular d-PET fluorescence-quenching mechanism transpiring between directly-linked electronically-uncoupled π-systems comprising its components. DFT calculations guided selection of a suitable fluorogenic scaffold and nitroaromatic moiety candidate that when adjoined could (i) afford such photophysical response upon bioreduction by upregulated NTR activity in hypoxic tumor cells/tissue and (ii) employ a retention mechanism strategy that capitalizes on an inherent physical property of the NIR fluorogenic scaffold for achieving signal amplification. NO 2 -Rosol demonstrated 705 nm NIR fluorescence emission and a 157 nm Stokes shift, selectivity for NTR over relevant bioanalytes, and a 28- and 12-fold fluorescence enhancement in solution and between cells cultured under different oxic conditions, respectively. Finally, in establishing feasibility for NO 2 -Rosol to provide favorable contrast levels in in solutioand in vitrostudies, we anticipate NO 2 -Rosol similarly doing so in future studies towards its translation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Soil pore architecture and rhizosphere legacy define N 2 O production in root detritusphere

Root detritusphere is one of the most important sources of N 2 O, however, understanding of how N 2 O emission from the detritusphere is influenced by soil properties remains elusive. Here, we evaluated the effects of pore architecture and soil moisture on N 2 O emission during the decomposition of in-situ grown roots of switchgrass, an important bioenergy crop. We combined dual isotope labeling ( 15 C and 15 N) with zymography to gain insights into the location of the microbial N 2 O production in soils with contrasting pore architectures. In the studied soil, the effect of soil pore architecture on N 2 O emissions was 6 times greater than that of soil moisture. Soil dominated by > 30 μm Ø pores (i.e., large-pore soil) had higher chitinase activity than the soil dominated by < 10 μm Ø pores (i.e., small-pore soil), especially near the decomposing roots. The chitinase activity on the decomposing roots was positively correlated with emission of root-derived N 2 O, indicating that N released from root decomposition was an important source of N 2 O. Greater N 2 O and N2 emission was induced by switchgrass roots in soils dominated by the large- compared to the small-pore soils. Here, the microenvironment developed near decomposing roots of the large-pore soil also resulted in positive N 2 O priming. Our study challenged the traditional view on soil moisture as the main factor of N 2 O production. Production and emission of N 2 O was most intensive in microbial activity hotspots (i.e., rhizosphere legacy) in the large pores, where decomposed roots release mineral N as the main N 2 O source.

13C Pulse labeling↗
DOE OSTI2023

Comparing the reaction profiles of single iron catalytic sites in enzymes and in reticular frameworks for methane-to-methanol oxidation

The design of synthetic inorganic catalysts mimicking the first coordination spheres of enzymatic cofactors often results in lower yields and selectivity than their biological counterparts. In this study, we exploit Kohn-Sham density functional methods to compare the reaction profiles of four single iron-based catalysts for the direct oxidation of methane to methanol: two biomimetic models based on two enzymes (cytochrome P450 and taurine dioxygenase [TauD]) and two synthetic reticular frameworks (iron-BEA zeolite and tri-iron oxo-center-based metal-organic framework). Both the biomimetic and inorganic catalysts show almost zero selectivity toward methanol for methane conversions >1% at ambient temperature. Furthermore, this study highlights that iron’s first coordination shell can influence selectivity toward methanol but to a limited extent. In the absence of methanol protection strategies, high selectivity can be reached only by mimicking the reaction microenvironment of enzymes beyond the first coordination shell of iron.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Engineering bimetallic interfaces and revealing the mechanism for carbon dioxide electroreduction to C 3+ liquid chemicals

Reduction reaction of CO 2 (CO 2 RR) to liquid C 3+ chemicals is a net-zero-carbon process and can increase local resiliency to power outages and fuel consumption. The mechanism and the catalyst design rules of CO 2 RR-to-C 3+ are unknown. Engineering bimetallic interface (e.g., Pd/Au) to tune the intermediate adsorption is promising for promoting C 3+ formation. Our density functional theory (DFT) calculations find that *CH 2 could be the key intermediate and C 1 -CH 2 coupling could be the rate-limiting step to generate C 3+ . High CO surface coverages can promote the bimetallic interfacial sites, lower the energetics of the C 1 -CH 2 coupling step, and enhance the C 3+ formation. We further construct a volcano plot of C 1 -CH 2 kinetics as a function of the binding strength of key intermediate *CH 2 via engineering the d-band center of the interfacial site. Our findings could guide the rational design of bimetallic interfaces and their near-surface microenvironment for enhancing CO 2 RR-to-C 3+ .

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2021

The role of vascular niche and endothelial cells in organogenesis and regeneration

Highlights: • The vascular niche creates a permissive environment that realize developmental or regenerative programs. • The proximity between endothelium and cells of organs suggests a role of endothelial cells in the organs maturation. • Organs provide cues shaping vascular network structure. The term vascular niche indicate the physical and biochemical microenvironment around blood vessel where endothelial cells, pericytes, and smooth muscle cells organize themselves to form blood vessels and release molecules involved in the recruitment of hematopoietic stem cells, endothelial progenitor cells and mesenchymal stem cells. The vascular niche creates a permissive environment that enables different cell types to realize their developmental or regenerative programs. In this context, the proximity between the endothelium and the new-forming cellular components of organs suggests an essential role of endothelial cells in the organs maturation. Dynamic interactions between specific organ endothelial cells and different cellular conponents are crucial for different organ morphogenesis and function. Conversely, organs provide cues shaping vascular network structure.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Antineoplastic activity of Salmonella Typhimurium outer membrane nanovesicles

Highlights: • ST-OMVs is a promising antitumor monotherapy or as an adjuvant to chemotherapies. • ST-OMVs downregulated Ki-67 and upregulated CD49b immune-expression. • ST-OMVs downregulated angiogenesis by inhibiting VEGF gene expression. • ST-OMVs increased tumor cells apoptosis and autophagy (increased caspase-3and Beclin1). Nano-sized Gram-negative bacterial outer membrane vesicles possess unique structural and immunostimulatory effects that could be exploited to regress tumors by alerting the host immune system and reversing the immunosuppressive tumor microenvironment. The current study was conducted to investigate the antitumor activity of the outer membrane vesicles (ST-OMVs) of Salmonella Typhimurium ATCC 14028, in vitro in human colorectal carcinoma (HTC116), breast cancer (MCF-7), and hepatocellular carcinoma (HepG2) cell lines and in vivo in Ehrlich solid carcinoma-bearing mice model either as a mono-immunotherapy or as an adjuvant to a commonly used conventional chemotherapy. In addition, we investigated the safety of ST-OMVs. Adult Swiss albino female mice with transplanted Ehrlich solid carcinoma were treated with either ST-OMVs, paclitaxel or a combination of both. Tumor volume, growth inhibition rate, quantitative RT-PCR of Bax and VEGF genes expression, histopathology and immune-expression of caspase-3, Beclin-1, CD49b and Ki-67 were all analyzed. Our results showed that ST-OMVs significantly decreased tumor volume, significantly increased tumor growth inhibition rate, up-regulated the immunohistochemical expression of caspase-3, Beclin-1, and CD49b (enhanced recruitment of NK cells). Furthermore, ST-OMVs down-regulated the expression of Ki-67, increased Bax gene expression and decreased VEGF gene expression as detected by qRT-PCR analysis. Histologically, ST-OMVs promoted apoptosis, decreased tumor invasion and mitotic activities. Moreover, ST-OMVs showed a remarkable cytotoxic activity in various investigated in vitro cancer cell lines. Our findings demonstrate potential antitumor activity of ST-OMVs that might be used as a promising safe antitumor immunotherapy or an adjuvant to conventional chemotherapeutic drugs, resolving some of their problems.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Hypoxia-cultured mouse mesenchymal stromal cells from bone marrow and compact bone display different phenotypic traits

Highlights: • Mouse compact bone is richer in MSC compared to central bone marrow. • Derivation of MSC from mouse compact bone is associated with lower risk of contamination with hematopoietic cells. • MSC from compact bone display higher osteogenic differentiation capacity than bone marrow MSC. It has been suggested that the bone marrow microenvironment harbors two distinct populations of mesenchymal stromal cells (MSC), one with a perivascular location and other present in the endosteum. A better understanding of the biology of these MSC subsets has been pursued in order to refine its clinical application. However, most comparative characterizations of mouse MSC have been performed in normoxia. This can result in misleading interpretations since mouse MSC subsets with low/defective p53 activity are known to be selected during culture in normoxia. Here, we report a comprehensive in vitro characterization of mouse MSC isolated from bone marrow (BM-MSC) and compact bone (CB-MSC) expanded and assayed under hypoxia for their morphology, clonogenic efficiency and differentiation capacity. We found that, under hypoxia, compact bone is richer in absolute numbers of MSC and isolation of MSC from compact bone is associated with a reduced risk of hematopoietic cell carryover. In addition, CB-MSC have higher in vitro osteogenic capacity than BM-MSC, while adipogenic differentiation potential is similar. These findings reinforce the hypothesis of the existence of MSC in bone marrow and compact bone representing functionally distinct cell populations and highlight the compact bone as an efficient source of murine MSC under physiological oxygen concentrations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

miRNAs: Critical mediators of breast cancer metastatic programming

Highlights: • This review highlights the crucial role played by miRNAs in the process of metastatic evolution of breast cancer. MicroRNA mediated aberrant gene regulation has been implicated in several diseases including cancer. Recent research has highlighted the role of epigenetic modulation of the complex process of breast cancer metastasis by miRNAs. miRNAs play a crucial role in the process of metastatic evolution by facilitating alterations in the phenotype of tumor cells and the tumor microenvironment that promote this process. They act as critical determinants of the multi-step progression starting from carcinogenesis all the way to organotropism. In this review, we focus on the current understanding of the compelling role of miRNAs in breast cancer metastasis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Organotypic platform for studying cancer cell metastasis

Highlights: • Liver and brain slices can be stable, realistic in vitro 3D models. • Cell stiffness and adhesion to the tissue play determinant roles in cellular invasion in 3D. • MEK inhibitors can lead to increased cell stiffness and adhesion forces, and consequently reduced cancer cell invasion. • MDA-MB-231 breast cancer cells migrate faster and deeper into brain tissue compared to liver tissue. Metastasis is the leading cause of mortality in cancer patients. To migrate to distant sites, cancer cells would need to adapt their behaviour in response to different tissue environments. Thus, it is essential to study this process in models that can closely replicate the tumour microenvironment. Here, we evaluate the use of organotypic liver and brain slices to study cancer metastasis. Morphological and viability parameters of the slices were monitored daily over 3 days in culture to assess their stability as a realistic 3D tissue platform for in vitro metastatic assays. Using these slices, we evaluated the invasion of MDA-MB-231 breast cancer cells and of a subpopulation that was selected for increased motility. We show that the more aggressive invasion of the selected cells likely resulted not only from their lower stiffness, but also from their lower adhesion to the surrounding tissue. Different invasion patterns in the brain and liver slices were observed for both subpopulations. Cells migrated faster in the brain slices (with an amoeboid-like mode) compared to in the liver slices (where they migrated with mesenchymal or collective migration-like modes). Inhibition of the Ras/MAPK/ERK pathway increased cell stiffness and adhesion forces, which resulted in reduced invasiveness. These results illustrate the potential for organotypic tissue slices to more closely mimic in vivo conditions during cancer cell metastasis than most in vitro models.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A HIF1A/miR-485–5p/SRPK1 axis modulates the aggressiveness of glioma cells upon hypoxia

The high aggressiveness of gliomas remains a huge challenge to clinical therapies, and the hypoxic microenvironment in the core region is a critical contributor to glioma aggressiveness. In this study, it was found that miR-485–5p was low expressed within glioma tissue samples and cells. GO enrichment annotation indicated that the predicted downstream targets miR-485–5p were enriched in hypoxia response and decreased oxygen level. In glioma cells, miR-485–5p overexpression suppressed cell viability, migratory ability, and invasive ability under both normoxic and hypoxic conditions. Through direct binding, miR-485–5p suppressed SRPK1 expression. Under hypoxia, SRPK1 overexpression enhanced hypoxia-induced glioma cell aggressiveness and significantly reversed the effects of miR-485–5p overexpression. Moreover, HIF1A could target the miR-485–5p promoter region to inhibit the transcription. HIF1A, miR-485–5p, and SRPK1 form a regulatory axis, which modulates glioma cell aggressiveness under hypoxia. In conclusion, we identify a HIF1A/miR-485–5p/SRPK1 axis that modulates the aggressiveness of glioma cells under hypoxia. The axis could potentially provide new research avenues in the treatment of gliomas considering the hypoxic environment in its core.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Culturing astrocytes on substrates that mimic brain tumors promotes enhanced mechanical forces

Highlights: • Human astrocytes increase traction forces of cells applied to the ECM in response to increased substrate stiffness. • Astrocytes apply intercellular stresses with noticeable increase in higher substrate stiffness. • Cell velocity decreases in human astrocytes in brain tumor like environment compared to normal brain environment. • Astrocytes mechanical strength and function could be potentially enhanced by increased stiffness of the microenvironment. Astrocytes are essential to brain homeostasis and their dysfunction can have devastating consequences on human quality of life. Such deleterious effects are generally due in part to changes that occur at the cellular level, which may be biochemical or biomechanical in nature. One biomechanical change that can occur is a change in tissue stiffness. Brain tumors are generally associated with increased brain tissue stiffness, but the impact increased tissue stiffness has on astrocyte biomechanical behavior is poorly understood. Therefore, in this study we cultured human astrocytes on flexible substrates with stiffness that mimicked the healthy human brain (1 kPa), meningioma (4 kPa), and glioma (11 kPa) and investigated astrocyte biomechanical behavior by measuring cell-substrate tractions, strain energies, cell-cell intercellular stresses, and cellular velocities. In general, tractions, intercellular stresses, and strain energy was observed to increase as a function of increased substrate stiffness, while cell velocities were observed to decrease with increased substrate stiffness. We believe this study will be of great importance to the fields of brain pathology and brain physiology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Genetically engineered mouse models of esophageal cancer

Esophageal cancer is the most common cause of cancer-related death worldwide with a diverse geographical distribution, poor prognosis, and diagnosis in advanced stages of the disease. Identification of the mechanisms involved in esophageal cancer development is evaluative to improve outcomes for patients. Genetically engineered mouse models (GEMMs) of cancer provide the physiologic, molecular, and histologic features of the human tumors to determine the pathogenesis and treatments for cancer, hence exhibiting a source of tremendous potential for oncology research. The advancement of cancer modeling in mice has improved to the extent that researchers can observe and manipulate the disease process in a specific manner. Despite the significant differences between mice and humans, mice can be great models for human oncology researches due to similarities between them at the molecular and physiological levels. Due to most of the existing esophageal cancer GEMMs do not propose an ideal system for pathogenesis of the disease, genetic risks, and microenvironment exposure, so identification of challenges in GEM modeling and well-developed technologies are required to obtain the most value for patients. In this review, we describe the biology of human and mouse, followed by the exciting esophageal cancer mouse models with a discussion of applicability and challenges of these models for generating new GEMMs in future studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Heterogeneous response of cancer-associated fibroblasts to the glucose deprivation through mitochondrial calcium uniporter

Highlights: • CAFs from a tumor mass are heterogeneous under the glucose deficient condition. • CAFs survive under glucose deficient condition by activation of TGF-β and calcium. • Calcium influx to mitochondria is critical for survival of glucose-deficient CAFs. • MCU in CAFs could be a feasible target for the development of anticancer drugs. Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have distinct features from normal fibroblasts (NFs). However, the discriminative nature of heterogeneous CAFs under glucose starvation remains unknown. In this study, we investigated the changes in the mitochondrial calcium concentration and relevant intracellular machinery in CAFs under glucose-deficient conditions. Xenografted tumor masses were dissected into multiple pieces and subjected to the CAF isolation using magnetically activated cell sorting (MACS). NFs were separated from the normal lung and skin. Under glucose starvation, CAFs from the tumor mass exhibited heterogeneity in cell proliferation, ATP production and calcium concentration. Compared to NFs, mitochondrial calcium concentration was significantly higher in glucose-starved CAFs with upregulation of mitochondrial calcium uniporter (MCU) that led to enhancement of ATP production and cell growth. Intriguingly, treatment of glucose-starved CAFs with oligomycin increased apoptosis by disrupted calcium homeostasis following overactivation of the mPTP. Moreover, oligomycin-induced apoptosis was mitigated by calcium chelation. This study demonstrated that the discriminative calcium influx to mitochondria through MCU coordinated cell growth and apoptosis in glucose-starved CAFs but not in NFs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Decellularized ECM derived from normal bone involved in the viability and chemo-sensitivity in multiple myeloma cells

Multiple myeloma (MM) is an incurable plasma cell malignancy. The progression of MM is closely related to the bone microenvironment. Bone matrix proteins are remodeled and manipulated to govern cancer growth during the process of MM. However the role of normal bone extracellular matrix in MM is still unclear. In this study the decellularized extracellular matrix derived from normal SD rats’ skulls (N-dECM) was prepared by decellularization technology. The CCK 8 assay and the dead-live cell kit assay were used to determine the viability of MM cells and the sensitivity to bortezomib. The Realtime PCR and Western blot assay were used to assay the mRNA and protein related to MM. Under the treatment of N-dECM, we found that the viability of MM cells was inhibited and the sensitivity of MM cells to bortezomib was increased. Additionally, the expression levels of APRIL and TACI, which participated in the progression of MM, were significantly decreased in MM cells. It suggested that N-dECM might inhibit the development of MM via APRIL-TACI axis, and our study may provide a novel and potential biomaterial for MM therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

The protein 4.1R downregulates VEGFA in M2 macrophages to inhibit colon cancer metastasis

Highlights: • Protein 4.1R knockout reduced the phagocytosis of M2 macrophages. • Co-culture with 4.1R knockout M2 macrophages enhances the malignancy of colon cancer. • Protein 4.1R knockout upregulates vascular endothelial growth factor A secreted by M2 macrophages. • Protein 4.1R knockout activates the PI3K/AKT signaling pathway and promotes the progression of colon cancer. M2 macrophages are crucial components of the tumour microenvironment and have been shown to be closely related to tumour progression. Co-culture with 4.1R{sup −/−} M2 macrophages enhances the malignancy of colon cancer (CC), but the mechanism remains unclear. Here, we report that protein 4.1R knockout reduced the phagocytosis of M2 macrophages (M-CSF/IL-4-treated bone marrow cells) and promoted MC38 colon cancer cell proliferation, migration, invasion, tumour formation and epithelial-mesenchymal transition (EMT), which are regulated by M2 macrophages. Further mechanistic dissection revealed that the 4.1R knockout upregulated vascular endothelial growth factor A (VEGFA) secreted by M2 macrophages and promoted colon cancer progression by activating the PI3K/AKT signalling pathway. In summary, our present study identified that 4.1R downregulates VEGFA secretion in M2 macrophages and delays the malignant potential of colon cancer by inhibiting the PI3K/AKT signalling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

DYNC1H1 regulates NSCLC cell growth and metastasis by IFN-γ-JAK-STAT signaling and is associated with an aberrant immune response

Highlights: • DYNC1H1 is upregulated and its high expression predicted poor outcomes in NSCLC. • Loss of function of DYNC1H1 inhibits cell growth and metastasis of NSCLC cells in vitro. • DYNC1H1 knockdown inhibited metastasis of NSCLC cells in vivo. • DYNC1H1 loss of function suppresses IFN-γ-JAK-STAT signaling pathway in NSCLC. • DYNC1H1 expression is correlated with aberrant immune response in NSCLC indicated by analysis of TCGA immune data. It is urgent to identify new biomarkers and therapeutic targets to ameliorate the clinical prognosis of patients with lung cancer. The functional significance and molecular mechanism of dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in nonsmall cell lung cancer (NSCLC) progression is still elusive. In our current study, publicly available data and Western blotting experiments confirmed that DYNC1H1 expression was upregulated in lung cancer samples compared with noncancerous samples. Quantitative real-time PCR (qPCR) results indicated that high DYNC1H1 expression in lung cancer tissues was significantly associated with clinical tumor stage and distal metastasis; moreover, its high expression was negatively correlated with prognosis. Functional experiments demonstrated that DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle, and promotion of both migration potential and invasion potential in vitro. Animal experiments by tail vein injection of lung cancer cells showed that DYNC1H1 knockdown significantly decreased lung cancer metastasis. Mechanistically, the results from a human protein array showed changes in the IFN-γ-JAK-STAT signaling pathway, and analysis of The Cancer Genome Atlas (TCGA) immune data demonstrated that disturbance of the immune microenvironment might be involved in the impaired growth and metastatic ability mediated by DYNC1H1 loss in NSCLC. DYNC1H1 might serve as a promising biological marker of prognosis and a potential clinical therapeutic target for patients with NSCLC.

60 APPLIED LIFE SCIENCES↗