Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiR-195 suppresses non-small cell lung cancer by targeting CHEK1.

ABSTRACT: MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome. Overexpression of miR-195 suppressed tumor cell growth, migration and invasion. We discovered that CHEK1 was a direct target of miR-195, which decreased CHEK1 expression in lung cancer cells. High expression of CHEK1 in lung tumors was associated with poor overall survival. Our results suggest that miR-195 suppresses NSCLC and predicts lung cancer prognosis.

SUBMITTER: Liu B

PROVIDER: S-EPMC4496229 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

MiR-195 suppresses non-small cell lung cancer by targeting CHEK1.

Liu Ben B Qu Jinli J Xu Fangxiu F Guo Yan Y Wang Yu Y Yu Herbert H Qian Biyun B

Oncotarget 20150401 11

MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissue ...[more]

PMID: 25840419

Similar Datasets

miR-195 potentiates the efficacy of microtubule-targeting agents in non-small cell lung cancer.

Project description:Microtubule-targeting agents (MTAs) are widely used for the treatment of non-small cell lung cancer (NSCLC). The response rate is only ?25%, mainly attributable to drug resistance. To identify determinants of resistance in NSCLC, we performed a high-throughput screen using a library of miRNA mimics. Here we report that miR-195 synergizes with MTAs to inhibit the growth of NSCLC cells in vitro, that increased expression of miR-195 sensitizes NSCLC cells to MTAs and that repression of miR-195 confers resistance to MTAs. We show that NSCLC tumors over-expressing miR-195 are more sensitive to MTA treatment and that induced expression of miR-195 in NSCLC tumors potentiates the anti-tumor effect of MTAs. Additionally, we demonstrate that miR-195 targets checkpoint kinase 1 (CHEK1) to regulate the response of NSCLC cells to MTAs, that over-expression of CHEK1 contributes to resistance to MTAs and that knock-down of CHEK1 synergizes with MTAs to repress cell growth. Our results highlight the importance of miR-195 in regulating the response of NSCLC cells to MTAs and underline the potential application of miR-195 as a biomarker for response to MTAs, and as a therapeutic adjuvant to MTA treatment.

| S-EPMC5953831 | biostudies-literature

MiR-199a-5p suppresses non-small cell lung cancer via targeting MAP3K11.

Project description:MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that directly target 3'UTR of mRNA, causing subsequent degradation or suppression of translation. Here, we verified that miR-199a-5p was significantly down-regulated in mouse NSCLC tissues and human patient samples. To further study the function of miR-199a-5p, lentivirus system was adopted to construct stably over-expressing miR-199a-5p A549, SPC-A1 and H1299 cell lines. Then, miR-199a-5p played a tumor suppression role via directly targeting MAP3K11 gene in non-small cell lung cancer (NSCLC). Elevated miR-199a-5p suppressed cell proliferation and arrested cell cycle in G1 phase. We found that MAP3K11 was negatively correlated with miR-199a-5p in NSCLC patient tissues and mouse xenograft tumors. Our results suggest that miR-199a-5p together with its target gene MAP3K11 is a key factor and constitutes a complicated regulation network in NSCLC.

| S-EPMC6584351 | biostudies-literature

miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2.

Project description:Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.

| S-EPMC6312350 | biostudies-literature

NF-?B-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by targeting MYO10.

Project description:Recently, dysregulation of microRNAs plays a critical role in cancer metastasis. Here, an in vivo selection approach was used to generate highly aggressive NSCLC sub-cell lines followed by comparing the microRNAs expression using microarrays. miR-124 was notably deregulated in both highly invasive sub-cell lines and node-positive NSCLC specimens. Over-expression of miR-124 robustly attenuated migration and metastatic ability of the aggressive cells. MYO10 was subsequently identified as a novel functional downstream target of miR-124, and was up-regulated in node-positive NSCLC tissues. Knockdown of MYO10 inhibited cell migration, whereas forced MYO10 expression markedly rescued miR-124-mediated suppression of cell metastasis. Additionally, we found an activated NF-?B-centered inflammatory loop in the highly aggressive cells leading to down-regulation of miR-124. These results suggest that NF-?B-regulated miR-124 targets MYO10, inhibits cell invasion and metastasis, and is down-regulated in node-positive NSCLC.

| S-EPMC4480748 | biostudies-literature

miR-512-5p suppresses the progression of non-small cell lung cancer by targeting β-catenin.

Project description:The oncogenic protein β-catenin is regulated by microRNAs (miRs) in non-small cell lung cancer (NSCLC). miR-512-5p is downregulated in NSCLC compared with healthy tissues and exhibits a tumour-suppressive effect. To study whether miR-512-5p acts on β-catenin to exert its anticancer effect in NSCLC, miR-512-5p mimic and inhibitor were transfected into NSCLC A549 and H1975 cells. miR-512-5p mimic inhibited the invasion of NSCLC cells and increased apoptosis, which suggested an inhibitory effect of miR-512-5p in NSCLC progression in vitro. By contrast, transfection with the miR-512-5p inhibitor resulted in the opposite effects. A dual-luciferase assay demonstrated that miR-512-5p complementarily bound to the 3'-untranslated region of β-catenin. miR-512-5p mimic suppressed the transcription and translation of β-catenin and reduced the expression of the downstream oncogenes cyclin D1 and matrix metalloproteinases, leading to the inhibition of Wnt/β-catenin signalling and subsequent inhibition of NSCLC tumourigenesis in vitro. In conclusion, miR-512-5p may function as a tumour suppressor in NSCLC by inhibiting the Wnt/β-catenin pathway.

| S-EPMC6923952 | biostudies-literature

miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene.

Project description:BackgroundMetastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Invadopodia, which are cancer-specific protrusive structures, play a crucial role in the metastatic cascade through degradation of the basement membrane and surrounding stroma. Cortactin, a critical component of invadopodia, frequently used as an invadopodia marker, a universally important player in invadopodia function, and is frequently overexpressed in cancer, but the exact mechanism of regulation is not yet fully understood.MethodsThe expression level of CTTN in human non-small cell lung cancer (NSCLC) tissues was detected by qRT-PCR. Cell migration, invasion and invadopodia formation were assessed in vitro by wound-healing, transwell assay and immunofluorescence, respectively. The dual-luciferase reporter assay was used to identify the direct target of miR-182.ResultsHepatocyte growth factor (HGF) and phorbol 12,13-dibutyrate (PDBu) can induce CTTN expression, motility, and invasion ability, as well as invadopodia formation in non-small cell lung cancer (NSCLC). Moreover, miR-182 suppressed metastasis and invadopodia formation by targeting CTTN in NSCLC. Our qRT-PCR results showed that CTTN expression was inversely correlated with miR-182 expression that suppressed invadopodia formation via suppression of the Cdc42/N-WASP pathway. Furthermore, miR-182 negatively regulated invadopodia function, and suppressed extracellular matrix(ECM) degradation in lung cancer cells by inhibiting cortactin.ConclusionCollectively, our results demonstrated that miR-182 targeted CTTN gene in NSCLC and suppressed lung cancer invadopodia formation, and thus suppressed lung cancer metastasis. This suggests a therapeutic application of miR-182 in NSCLC.

| S-EPMC6038252 | biostudies-literature

miR-195-5p Suppresses Lung Cancer Cell Proliferation, Migration, and Invasion Via FOXK1.

Project description:Lung cancer remains one of the leading causes of cancer deaths around the world. Previous studies have shown that microRNAs have pivotal functions in tumorigenesis including lung cancer. It is reported that microRNA-195-5p acts as a tumor suppressor role in human cancers. However, the function and molecular mechanism of microRNA-195-5p in lung cancer progression is still unclear. In the present study, the results showed that the expression of microRNA-195-5p was downregulated both in lung cancer tissues and in lung cancer cell lines. Enhanced expression of microRNA-195-5p inhibited cell proliferation, migration, and invasion in lung cancer cells. Furthermore, Forkhead box k1 was identified as the direct target of microRNA-195-5p. Forkhead box k1 overexpression could restore the repressed cell proliferation and metastasis caused by microRNA-195-5p overexpression. Our results demonstrated that a functional mechanism of microRNA-195-5p in regulating lung cancer. It indicates that microRNA-195-5p may regulate lung cancer growth and metastasis through the regulation of Forkhead box k1, highlighting the potential application for the treatment of lung cancer in the future.

| S-EPMC7238777 | biostudies-literature

By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer.

Project description:Ku80 is involved in DNA double-strand breaks (DSBs) repair. Ku80 is overexpressed in lung cancer tissues, yet, molecular mechanisms have not been examined. We identified that miRNA, hsa-miR-526b, is bound to the 3'-UTR of Ku80 mRNA, thus decreasing Ku80 expression in NSCLC cells. Hsa-miR-526b was downregulated in NSCLC tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Overexpression of Ku80 and downregulation of hsa-miR-526b were associated with poor clinical outcomes of NSCLC patients. Hsa-miR-526b suppressed NSCLC cell proliferation, clonogenicity, and induced cell cycle arrest and apoptosis. Hsa-miR-526b inhibited xenografts and orthotopic lung tumor growth. Further, Ku80 knockdown in NSCLC cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-526b overexpression. In agreement, Ku80 restoration partially reversed cell cycle arrest and apoptosis induced by hsa-miR-526b in NSCLC cells in vitro and in vivo. In addition, hsa-miR-526b overexpression or Ku80 knockdown increased p53 and p21CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential target in cancer therapy.

| S-EPMC4359307 | biostudies-literature

MiR-302a-5p suppresses cell proliferation and invasion in non-small cell lung carcinoma by targeting ITGA6.

Project description:MicroRNA-302a-5p (miR-302a-5p) has been implicated in several cancers; however, its role in human non-small cell lung carcinoma (NSCLC) remains unknown. In this study, we showed that miR-302a-5p is downregulated in NSCLC tissues and cell lines. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays showed that overexpression of a miR-302a-5p mimic suppressed NSCLC cell proliferation, which was confirmed by the results of a cell cycle assay. Overexpression of miR-302a-5p also reduced the migration and invasion of NSCLC cells. Additionally, miR-302a-5p overexpression significantly inhibited NSCLC growth and metastasis in a mouse xenograft model. With regard to the underlying mechanism, integrin α6 (ITGA6) mRNA was shown to be a novel target of miR-302a-5p, and overexpression of ITGA6 attenuated the inhibitory effects of miR-302a-5p on the proliferation and migration of NSCLC cells. In clinical NSCLC samples, miR-302a-5p expression was negatively correlated with ITGA6 expression, which was high in the samples. Collectively, these results indicate that miR-302a-5p acts as a tumor suppressor in NSCLC by directly targeting ITGA6 mRNA and may be useful as a theranostic biomarker of NSCLC.

| S-EPMC6684888 | biostudies-other

Rac1 targeting suppresses human non-small cell lung adenocarcinoma cancer stem cell activity.

Project description:The cancer stem cell (CSC) theory predicts that a small fraction of cancer cells possess unique self-renewal activity and mediate tumor initiation and propagation. However, the molecular mechanisms involved in CSC regulation remains unclear, impinging on effective targeting of CSCs in cancer therapy. Here we have investigated the hypothesis that Rac1, a Rho GTPase implicated in cancer cell proliferation and invasion, is critical for tumor initiation and metastasis of human non-small cell lung adenocarcinoma (NSCLA). Rac1 knockdown by shRNA suppressed the tumorigenic activities of human NSCLA cell lines and primary patient NSCLA specimens, including effects on invasion, proliferation, anchorage-independent growth, sphere formation and lung colonization. Isolated side population (SP) cells representing putative CSCs from human NSCLA cells contained elevated levels of Rac1-GTP, enhanced in vitro migration, invasion, increased in vivo tumor initiating and lung colonizing activities in xenografted mice. However, CSC activity was also detected within the non-SP population, suggesting the importance of therapeutic targeting of all cells within a tumor. Further, pharmacological or shRNA targeting of Rac1 inhibited the tumorigenic activities of both SP and non-SP NSCLA cells. These studies indicate that Rac1 represents a useful target in NSCLA, and its blockade may have therapeutic value in suppressing CSC proliferation and metastasis.

| S-EPMC3036726 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data