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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 505 records · Page 28
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

TINCR facilitates non-small cell lung cancer progression through BRAF-activated MAPK pathway

Highlights: • TINCR facilitates NSCLC. • TINCR interacts with BRAF. • TINCR activates MAPK by BRAF. Long non-coding RNAs are critically involved in oncogenesis in various cancer types. Here we reported a novel lncRNA signature correlated with progression of non-small cell lung cancer (NSCLC). In particular, we identified elevated expression of terminal differentiation-induced noncoding RNA (TINCR) in human NSCLC samples, which were associated with enhanced migration, viability in NSCLC cells in vitro. Higher TINCR level was also correlated with poor survival. Furthermore, TINCR increased xenograft tumor growth in vivo mouse models. Mechanistic study demonstrated that TINCR can interact with BRAF to facilitate its kinase activity, thereby leading to activation of oncogenic mitogen-activated protein kinase (MAPK) pathway. These results suggested that TINCR upregulation may signal through the MAPK pathway to promote NSCLC tumorigenesis. Therefore, TINCR may serve as a potential prognostic marker and therapeutic target for NSCLC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-196b is a prognostic factor of human laryngeal squamous cell carcinoma and promotes tumor progression by targeting SOCS2

Highlights: • Aberrant expression of miR-196b and SOCS2 were found in LSCC samples. • MiR-196b can directly inhibit SOCS2 expression in LSCC cells in vitro. • MiR-196b promotes LSCC cells proliferation and invasion by inhibiting SOCS2. • MiR-196b/SOCS2 pathway are correlated with LSCC progression in clinic. • MiR-196b serves as an effective prognostic factor of LSCC. Laryngeal squamous cell carcinoma (LSCC) has the second highest incidence among the head and neck malignancies. Additionally, the incidence of LSCCs has been recently increasing. Therefore, understanding the mechanisms of LSCC tumorigenesis and identifying novel biomarkers to accurately predict and improve the prognosis of patients with LSCC is extremely important.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression

Highlights: • The prognostic value of m{sup 6}A methyltransferase and demethylase in lung cancer. • Differentially expressed FTO accounts for the aberrant m{sup 6}A modification in LUSC. • FTO acts as an oncogene in LUSC. • MZF1 mediates FTO regulation in LUSC. N{sup 6}-Methyladenosine (m{sup 6}A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m{sup 6}A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m{sup 6}A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m{sup 6}A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m{sup 6}A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m{sup 6}A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

RHCG suppresses cervical cancer progression through inhibiting migration and inducing apoptosis regulated by TGF-β1

Highlights: • Expression of RHCG is associated with human cervical cancer development. • RHCG regulates migration and apoptosis in human cervical cancer cell lines. • RHCG modulates TGF-β1 expressions to reduce migration and induce apoptosis in human cervical cancer cell lines. Cervical cancer is the second commonest cancer among women in the worldwide, and the majority cause of death in various countries, highlighting the importance of investigating new therapeutic targets. Rh family, C glycoprotein (RHCG) belongs to the Rhesus (Rh) family and was first identified as Rh blood group antigens. It has been confirmed to function in cancer progression, including prostate cancer and esophageal squamous cell carcinoma. However, its role in cervical cancer has never been explored. The present study indicated that RHCG was down-regulated in cervical cancers compared to that in normal cervical tissues, and further decreased in cervical cancer cell lines. Functionally, RHCG overexpression reduced cervical cancer cell proliferation and migration, as evidenced by the decreased transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-2 and MMP-9 expressions in cancer cells; however, an opposite effect was observed when RHCG was knocked down. Further, increase of RHCG markedly induced apoptosis in cervical cancer cells by improving the cleavage of Caspase-3 and poly (ADP-Ribose) polymerase (PARP). And cells transfected with RHCG siRNA exhibited a notable reduction of cleaved Caspase-3 and PARP. Moreover, nucleus nuclear factor-κB (NF-κB) and whole cell xIPA expressions were markedly reduced by over-expressing RHCG. Conversely, suppressing RHCG elevated NF-κB activation and xIPA expression in cervical cancer cells. Notably, we found that TGF-β1 treatment could abolish the effects of RHCG over-expression on the reduction of cell migration and enhancement of apoptosis in cervical cancer cells. Over-expressing RHCG-reduced NF-κB activation and xIPA expression were also abrogated by TGF-β1 pre-treatment. Additionally, enhancing NF-κB activity could restore xIPA expressions and decrease apoptotic response in cervical cancer cells over-expressing RHCG. In vivo, we also found that RHCG over-expression reduced cervical tumor growth through the same signaling pathways as we found in vitro. Therefore, RHCG may be a potential prognostic biomarker and therapeutic target for human cervical cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

l-asparaginase induces intrinsic mitochondrial-mediated apoptosis in human gastric adenocarcinoma cells and impedes tumor progression

Highlights: • We first confirmed that l-asparagine is essential for the growth and proliferation of AGS cells. • We further clarified that l-asparagine deprivation by l-asparaginase promotes anti-proliferation and apoptosis of AGS cells. • We demonstrated that action of l-asparaginase alters mitochondrial membrane permeability and activates intrinsic apoptosis. • We also showed that l-asparaginase impedes tumor progression. l-asparagine essentially regulates growth and proliferation of cancer cells. l-asparaginase is an anti-cancer enzyme that deprives the cancer cells of l-asparagine. The purpose of this study was to explore the mechanism of a novel l-asparaginase from Pseudomonas fluorescens on l-asparagine deprivation mediated anti-proliferation, apoptosis in human gastric adenocarcinoma cells and to evaluate inhibition of angiogenesis. We observed that, the presence of extracellular l-asparagine was essential for the growth of AGS cells. l-asparagine deprivation by l-asparaginase induced metabolic stress, cytotoxicity and apoptosis by G0 phase cell-cycle arrest, modulated the mitochondrial membrane integrity, accelerated caspase-3 activation and instigated DNA damage. The RT-PCR analysis of pro-apoptosis genes: bak1, bax, bbc3, bik, pmaip1, bnip3l, apaf1, casp3, casp7 and casp9 were significantly higher (P xiap, bid, mcl1, and death receptor genes tnf and tradd were significantly down-regulated (P l-asparaginase alters mitochondrial membrane permeability and auxiliary activates intrinsic apoptosis. Therefore, this mechanistic approach might be considered as a targeted enzymotherapy against gastric adenocarcinoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA circ-BANP-mediated miR-503/LARP1 signaling contributes to lung cancer progression

Recently, circular RNAs (circRNAs) attract much attention due to their potential vital functions in multiple human diseases, including cancer. circ-BANP has been reported to modulate colorectal cancer growth. Nevertheless, the relationship between circ-BANP and lung cancer requires to be investigated. In this study, we found circ-BANP was overexpressed in lung cancer tissues. Higher circ-BANP expression was associated with lower survival rate. Moreover, silencing circ-BANP markedly inhibited proliferation, migration and invasion of lung cancer cells in vitro and impaired tumor propagation in vivo. In mechanism, circ-BANP was identified as the sponge of miR-503 while miR-503 targets LARP1. Circ-BANP-induced inhibition of miR-503 led to increased expression of LARP1 in lung cancer. Finally, rescue assays indicated that LARP1 restoration partially reversed the effects of circ-BANP knockdown in lung cancer. In sum, our study illustrated that circ-BANP-mediated miR-503/LARP1 signaling promoted lung cancer growth, migration and invasion, providing a novel insight on the mechanism underlying lung cancer progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

DNA copy number gain-mediated lncRNA LINC01061 upregulation predicts poor prognosis and promotes papillary thyroid cancer progression

Several DNA copy number amplifications (CNAs) have been reported in papillary thyroid cancer (PTC). However, the functional role of CNAs in PTC remains very unclear. And whether there is a correlation between long noncoding RNA (lncRNA) and CNA requires to be explored. Here, we identified a novel lncRNA LINC01061. The genomic copy number of LINC01061 is amplified, which leads to its elevated expression level in PTC tissues. Moreover, increased level of LINC01061 was correlated with aggressive clinicopathological characteristics. Functional study indicated that LINC01061 silence significantly inhibited the proliferation, cell-cycle and invasion of PTC cells in vitro and tumor growth in vivo. Mechanistically, we showed that LINC01061 interacted with miR-4316 to promote E2F6 expression. The expression of miR-4316 was downregulated in PTC tissues while that of E2F6 was upregulated. Through rescue assay, we demonstrated that LINC01061 promoted PTC cell proliferation, cell-cycle progression and invasion by regulating miR-4316/E2F6 signaling pathway. In conclusion, our research indicated that LINC01061 might be a target for PTC therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Decreased expression of protein tyrosine kinase 6 contributes to tumor progression and metastasis in laryngeal squamous cell carcinoma

Highlights: • Overexpression of PTK6 significantly decreased cell growth, clonogenicity, invasion and migration capacity in LSCC. • PTK6 suppresses LSCC proliferation mainly by inhibiting c-myc and cyclinD1 expression. • PTK6 promotes cell apoptosis in LSCC. • PTK6 mitigated LSCC invasion and migration through regulating EMT and MMP-9. PTK6 is involved in cell proliferation, invasion and migration. Patients with lower PTK6 expression predicts poor prognosis of LSCC. However, the mechanism of PTK6 in LSCC progression remains unclear. We investigated the role of PTK6 in the pathogenesis of LSCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-181d-5p-FOXP1 feedback loop modulates the progression of osteosarcoma

MicroRNAs (miRNAs) are playing more and more fundamental roles in the progress of human cancers. miR-181d-5p has not been fully elucidated in human cancers. In this study, we aimed to investigate the biological function and mechanism of miR-181d-5p in osteosarcoma (OS). At first, the expression conditions of miR-181d-5p were identified in OS tissues and cell lines. Downregulation of miR-181d-5p was identified to be a significant prognostic factor for patients with OS. Using the bioinformatics analysis, the putative target mRNA (FOXP1) of miR-181d-5p was found out. Similarly, the expression conditions and prognostic value of FOXP1 were identified in OS. To validate the tumor suppressive role of miR-181d-5p in OS, gain or loss of function assays were carried out in OS cell lines. The results indicated the anti-oncogenic function of miR-181d-5p in OS. Subsequently, the oncogenic function of FOXP1 in OS was identified by functional assays. Rescue assays manifested that the oncogenic function of FOXP1 can be partially reversed by miR-181d-5p. Combining with the result of luciferase reporter assay, we confirmed that miR-181d-5p can act as a tumor suppressor in OS via targeting FOXP1. Further mechanism experiments revealed that FOXP1 can suppressed the transcription activity of miR-181d-5p by acting as a transcription inhibitor. In conclusion, our study revealed that miR-181d-5p-FOXP1 feedback loop modulates cell proliferation and metastasis in osteosarcoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling

Emerging evidences show RNA back-splicing produces a new type of noncoding RNA, namely circular RNA (circRNA). Many reports demonstrate that circRNA circHIPK3 exerts oncogenic or anti-tumor roles in different cancers, such as ovarian cancer, bladder cancer, osteosarcoma, colorectal cancer and liver cancer. However, no study about circHIPK3 function in glioma exists until today. In this study, we showed that circHIPK3 was upregulated in glioma tissues. Elevated level of circHIPK3 was linked to poor prognosis. Functional investigation indicated that circHIPK3 promotes glioma cell proliferation and invasion, and tumor propagation in vivo. Furthermore, miR-654 was identified as a target of circHIPK3 while IGF2BP3 was targeted by miR-654. CircHIPK3 could promote IGF2BP3 expression via interacting with miR-654 in glioma cells. Finally, CCK8 and transwell assays illustrated that IGF2BP3 overexpression could reverse the effects of IGF2BP3 depletion. Altogether, our findings demonstrated that circHIPK3 contributes to glioma progression through targeting miR-654 from IGF2BP3 and implies circHIPK3 might be a potential target for glioma therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA LINC00641 predicts prognosis and inhibits bladder cancer progression through miR-197-3p/KLF10/PTEN/PI3K/AKT cascade

As a new group of important effector molecules involved in multiple cancers, long noncoding RNAs (lncRNAs) have attracted much attention recently. Especially, evidences have indicated lncRNAs might be promising biomarkers and targets for cancer therapy. LINC00641 is a novel lncRNA, whose function remains totally unclear. The aim of our study was to determine the functions of LINC00641 in bladder cancer. We found that LINC00641 expression was significantly down-regulated in bladder cancer tissues. Down-regulation of LINC00641 in patients with bladder cancer predicts poor prognosis. Gain-of-function assays indicated that LINC00641 up-regulation markedly inhibited the proliferation, migration and invasion of bladder cancer cells. Xenograft assay also confirmed that LINC00641 overexpression suppressed bladder cancer growth in vivo. Mechanistically, LINC00641 was demonstrated to interact with miR-197-3p, whose target was KLF10. By up-regulating KLF10 level, LINC00641 suppressed the PTEN/PI3K/AKT pathway, leading to prevention of bladder cancer progression. Taken together, our study illustrated a novel signaling cascade of LINC00641/miR-197-3p/KLF10/PTEN/PI3K/AKT pathway regulating bladder cancer development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA HAND2-AS1 sponging miR-1275 suppresses colorectal cancer progression by upregulating KLF14

Long noncoding RNAs (lncRNAs) represent a novel type of noncoding RNAs of over 200 nucleotides, characterized by no or limited protein-coding potential. Although the function of lncRNAs attracts increasing attention recently, the relationship between lncRNA and colorectal cancer (CRC) remains further investigation. In our study, we found that lncRNA HAND2-AS1 was markedly downregulated in CRC tissues. And its expression level was negatively correlated with metastasis and advanced stage in CRC patients. Furthermore, we showed that HAND2-AS1 low expression predicted poor prognosis. Functionally, we found that overexpression of HAND2-AS1 obviously attenuated the proliferation and invasion of CRC cells. Ectopic expression of HAND2-AS1 also inhibited tumor propagation in vivo. In mechanism, HAND2-AS1 served as a sponge of miR-1275 which targeted KLF14. Through facilitating KLF14 expression, HAND2-AS1 suppressed CRC progression. In conclusion, our study demonstrated that HAND2-AS1 exerts a suppressive role in CRC by sponging miR-1275 and modulating KLF14 expression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Upregulated circular RNA circ{sub 0}016760 indicates unfavorable prognosis in NSCLC and promotes cell progression through miR-1287/GAGE1 axis

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with increasing worldwide incidence and is characterized by dismal prognosis due to its early recurrence and metastasis. Accumulating evidence documented that aberrantly expressed circular RNAs (circRNAs) are critically involved in tumorigenesis. In the current study, we focused on a novel circRNA, circ{sub 0}016760 in NSCLC. qRT-PCR was carried out to determine the expression level of circ{sub 0}016760 in tissue samples and cell lines. The clinical value of circ{sub 0}016760 was also investigated. The functions of circ{sub 0}016760 was explored by CCK-8, colony formation, flow cytometry, Transwell and animal experiments. Luciferase reporter assays were conducted to investigate the association between circ{sub 0}016760 and miR-1287 and miR-1287 and GAGE1. We found that circ{sub 0}016760 was enhanced in NSCLC tissues and cells and the upregulation of circ{sub 0}016760 is associated with advanced TNM stages, lymph node metastasis and adverse prognosis in NSCLC patients. Moreover, circ{sub 0}016760 could significantly promote cell growth and metastatic properties and inhibit cell apoptosis in NSCLC cells. In mechanism, circ{sub 0}016760 functioned as a sponge for miR-1287 and regulated the expression of GAGE1. Subsequently, functional assays illustrated that the oncogenic properties of circ{sub 0}016760 is partly attribute to the regulation of miR-1287/GAGE1 axis. In summary, circ{sub 0}016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis and progression of NSCLC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Ramalin, an antioxidant compound derived from Antarctic lichen, prevents progression of liver fibrosis induced by dimethylnitrosamine (DNM) in rats

Highlights: • New chemical substance, “Ramalin”, derived from Antarctic lichen, acts as a powerful antioxidant and ROS scavenger. • Ramalin significantly reduces hepatic stellet cell activation, while also reducing malondialdehyde (MDA), and hydroxyproline (HP). • Ramalin offers hepatoprotection effect by ameliorating DMN-induced oxidative stress and hepatotoxicity. Hepatic fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM), primarily collagen, within the liver. Because reactive oxygen species (ROS) has been implicated in its pathogenesis, the use of antioxidants as a potential treatment has been broadly explored. Here, we investigated the hepatoprotective properties of ramalin (RM), a compound extracted from the Antarctic lichen Ramalina terebrata, against hepatic fibrosis in vitro and in vivo. RM suppressed hepatic stellate cell (HSC) activation in vitro without any significant signs of adverse effects on the cells tested, and the accumulation of ECM was dramatically reduced in the liver tissue. Oral administration of RM in rats noticeably improved the gross appearance of the liver with increased body and liver weight relative to the DMN injected rats, and all of the serum biochemical markers returned to the normal range. RM treatment have ameliorated hepatic fibrosis in rats induced by DMN by repressing α-smooth muscle actin (α-SMA) and upregulating heme oxygenase-1 (HO-1). In addition, RM significantly reduced collagen accumulation, and levels of malondialdehyde (MDA) and hydroxyproline (HP) in the liver tissue of DMN injected rats. The efficacy exerted by RM was through erythroid 2–related factor 2 (Nrf2) mediated antioxidant response proteins such as HO-1 and NAD(P)H quinone dehydrogenase 1 (NQO-1). Our results show the beneficial effect of RM against the progression of hepatic fibrosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA{sub 1}00290 promotes colorectal cancer progression through miR-516b-induced downregulation of FZD4 expression and Wnt/β-catenin signaling

Accumulating evidence indicates that circular RNAs (circRNA) exert crucial functions in the development and advance of cancers. CircRNA{sub 1}00290 has been reported to promote proliferation in oral cancer. However, whether it participates in colorectal cancer (CRC) remains unclear. Here, our report showed that circRNA{sub 1}00290 level was significantly increased in CRC tissues and cell lines. Besides, circRNA{sub 1}00290 expression was positively correlated with tumor metastasis while inversely correlated with prognosis. Silencing circRNA{sub 1}00290 markedly reduced cell proliferation rate, inhibited migration and invasion abilities, but promoted apoptosis in vitro. Mechanistically, our data revealed circRNA{sub 1}00290 was a competing endogenous RNA (ceRNA) of FZD4 by sponging miR-516b, leading to activation of Wnt/β-catenin pathway. Rescue assay indicated that FZD4-induced activation of β-catenin pathway is indispensable for the function of circRNA{sub 1}00290 in CRC. In summary, our study for the first time revealed a novel regulatory loop of circRNA{sub 1}00290/miR-516b/FZD4/Wnt/β-catenin implicated in CRC progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MicroRNA-128 contributes to the progression of gastric carcinoma through GAREM-mediated MAPK signaling activation

Gastric carcinoma (GC) represents the most common malignant cancer and the second leading cause of cancer death worldwide. However, the molecular mechanisms and biological progression of GC remain unknown. In this study, we found that miR-128 is a critical tumor suppressor that is downregulated in GC patients and GC cells and that GAREM is a direct downstream target of miR-128. Overexpression of miR-128 in HGC-27 and MKN-45 cells resulted in suppressed cell growth and promoted cell apoptosis through a GAREM-dependent mechanism. Moreover, the precise mechanisms underlying the antitumor effect of miR-128 in GC are at least partially due to suppressing activation of the MAPK signaling pathway, induced by suppressing GAREM expression. This study is the first to demonstrate that the miR-128-GAREM-MAPK signaling pathway forms a critical feedback loop and mediates GC development, and these findings might demonstrate a potential therapeutic strategy for GC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

RBM17 controls apoptosis and proliferation to promote Glioma progression

Highlights: • RBM17 overexpressed in glioma patients and resulted in the poor prognosis. • Downregulation of RBM17 suppressed proliferation and induced apoptosis in glioma cells. • The silencing of RBM17 in U87 cells suppressed the tumor growth in vivo. • RBM17 on main signaling pathways in human glioma cells. The splicing factor SPF45 (RBM17) is a well-known component of the spliceosome that is involved in alternative splicing. RBM17 is frequently overexpressed in many tumors and plays a crucial role in cancer progression and drug resistance. However, the role of RBM17 in the development of glioma has not been thoroughly elucidated to date. In the present study, we found that RBM17 was overexpressed in glioma and that a high level of expression of RBM17 was closely associated with a poor prognosis in glioma patients. We investigated the effect of RBM17 on apoptosis, cell growth and cell cycle indexes and the activation of apoptosis signaling by shRNA in human U87 and U251 glioma cells. The downregulated expression of RBM17 mRNA was accompanied by the induction of cell cycle arrest, and apoptosis, reduced cell proliferation in the two cell lines, and reduced cell survival, as measured by the increased activation of caspase-3, caspase-9, and PARP (poly ADP-ribose polymerase). Furthermore, in subcutaneous U87 cell xenograft tumors in nude mice, intradermal administration of an shRNA targeting RBM17 significantly downregulated RBM17 expression in vivo and was accompanied by the suppressed growth of glioma. To the best of our knowledge, our results are the first to confirm that RBM17 functions in promoting cell proliferation, affecting the cell cycle, and inducing apoptosis in human glioma cells both in vitro and in vivo. These results indicate that RBM17 may be a therapeutic target in the clinical management of glioma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

microRNA-9 selectively targets LMX1A to promote gastric cancer cell progression

Highlights: • miR-9 overexpression downregulates LMX1A, promoting gastric cancer (GC) cell proliferation. • miR-9 inhibition upregulates LMX1A to induce GC cell apoptosis. • LMX1A is the direct and primary target of miR-9 in GC cells. • miR-9 upregulation in human GC tissues correlates with LMX1A downregulation. LIM homeobox transcription factor 1, alpha (LMX1A) is downregulated in human gastric cancer (GC), functioning as a tumor suppressor. The current study aims to identify specific microRNA that can regulate LMX1A expression. By sequence analysis of LMX1A mRNA 3′-untranslated region (3′-UTR), we show that microRNA-9 (miR-9) putatively targets human LMX1A. In established (AGS cells) and primary human GC cells, ectopic overexpression of miR-9 by a lentiviral construct decreased LMX1A 3′-UTR activity, causing LMX1A mRNA and protein downregulation. Functional analyses show that miR-9 overexpression enhanced GC cell survival and proliferation. On the contrary, miR-9 inhibition by antagomir-9 lentivirus increased LMX1A 3′-UTR activity to upregulate LMX1A mRNA and protein expression, causing GC cell apoptosis. CRISPR/Cas9-mediated LMX1A knockout promoted AGS cell survival and proliferation. Importantly, miR-9 and antagomiR-9 were ineffective to the function of LMX1A-knockout AGS cells. In human GC tissues miR-9 is upregulated, which is negatively correlated with LMX1A downregulation. Together, we conclude that miR-9 selectively targets LMX1A to promote GC cell progression.

60 APPLIED LIFE SCIENCES↗