Dataset Information

MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/?-catenin axis in non-small-cell lung cancer.

ABSTRACT: MicroRNAs have been reported to play critical roles in the regulation of non-small-cell cancer (NSCLC) development, but the role of microRNA (miR)-331-3p in NSCLC is still unclear. In this study, the expression levels of miR-331-3p in NSCLC tumor tissues and adjacent normal tissues were examined by quantitative RT-PCR, and the relationship between miR-331-3p expression and patient clinicopathological characteristics was analyzed. The effects of miR-331-3p on epithelial-mesenchymal transition (EMT), migration, and metastasis of NSCLC cells were determined in vitro and vivo. Direct functional targets of miR-331-3p were identified by luciferase reporter assay, western blot assay, immunohistochemical staining, and rescue assay. The downstream pathway regulated by miR-331-3p was identified by immunofluorescence, immunoprecipitation, and Rac1 activity examination. Our results showed that miR-331-3p was significantly downregulated in NSCLC tumor tissues and was correlated with clinicopathological characteristics, and miR-331-3p could be an independent prognostic marker for NSCLC patients. Furthermore, miR-331-3p significantly suppressed EMT, migration and metastasis of NSCLC cells in vitro and in vivo. Both ErbB2 and VAV2 were direct functional targets of miR-331-3p. The activities of Rac1, PAK1, and ?-catenin were regulated by miR-331-3p through ErbB2 and VAV2 targeting. These results indicated that miR-331-3p suppresses EMT, migratory capacity, and metastatic ability by targeting ErbB2 and VAV2 through the Rac1/PAK1/?-catenin axis in NSCLC.

SUBMITTER: Li X

PROVIDER: S-EPMC6550127 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β-catenin axis in non-small-cell lung cancer.

Li Xizhe X Zhu Jiali J Liu Yuanqi Y Duan Chaojun C Chang Ruimin R Zhang Chunfang C

Cancer science 20190429 6

MicroRNAs have been reported to play critical roles in the regulation of non-small-cell cancer (NSCLC) development, but the role of microRNA (miR)-331-3p in NSCLC is still unclear. In this study, the expression levels of miR-331-3p in NSCLC tumor tissues and adjacent normal tissues were examined by quantitative RT-PCR, and the relationship between miR-331-3p expression and patient clinicopathological characteristics was analyzed. The effects of miR-331-3p on epithelial-mesenchymal transition (EM ...[more]

PMID: 30955235

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Project description:The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression of tumors. miRNAs and their target molecules are utilized for molecular diagnosis of urothelial carcinoma. NACC1 is one of several putative target molecules of miR-331-3p, and is associated with cell proliferation in cancers such as prostate and cervical cancer. Functional experiments involving miR-331-3p and its target molecule NACC1 were conducted using the urothelial carcinoma (UC) cell lines, T24, UMUC6, and KU7. Furthermore, quantitative reverse transcription polymerase chain reaction and immunostaining were performed to evaluate the expression of NACC1 in UC derived from transurethral resection of bladder tumor (TUR-Bt) specimens. The methane thiosulfonate (MTS) assay revealed that cell proliferation was significantly reduced after transient transfection of miR-331-3p precursor and/or NACC1 siRNA in UC cells. Cell senescence via cell cycle arrest at the G1 phase was induced by NACC1 inhibition. On the other hand, suppression of NACC1 induced cell migration and invasion abilities. Immunohistochemical analysis of TUR-Bt specimens revealed that over 70% of UC cells presented strongly positive results for NACC1. In contrast, normal urothelial cells were weakly positive for NACC1. It was also found that NACC1 expression was lower in invasive UC cells than in non-invasive UC cells. Loss of NACC1 induced vessel invasion in invasive UC tissues. The present results indicate that NACC1 regulated by miR-331-3p contributes to cell proliferation, and is involved in cell migration and invasion. This suggests that NACC1 can serve as a potential target molecule for the prediction and prognosis of UC, and can contribute to effective treatment strategies.

Project description:Aberrant expression of microRNAs (miRNAs) is involved in the development and progression of various types of cancers. In this study, we investigated the role of miR-331-3p in cell proliferation and the expression of keratinocyte differentiation markers of uterine cervical cancer cells. Moreover, we evaluated whether neuropilin 2 (NRP2) are putative target molecules that regulate the human papillomavirus (HPV) related oncoproteins E6 and E7. Cell proliferation in the human cervical cancer cell lines SKG-II, HCS-2, and HeLa was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cellular apoptosis was measured using the TdT-mediated dUTP nick end labeling (TUNEL) and Annexin V assays. Quantitative RT-PCR was used to measure the messenger RNA (mRNA) expression of the NRP2, E6, E7, p63, and involucrin (IVL) genes. A functional assay for cell growth was performed using cell cycle analyses. Overexpression of miR-331-3p inhibited cell proliferation, and induced G2/M phase arrest and apoptosis in SKG-II, HCS-2 and HeLa cells. The luciferase reporter assay of the NRP2 3'-untranslated region revealed the direct regulation of NRP2 by miR-331-3p. Gene expression analyses using quantitative RT-PCR in SKG-II, HCS-2, and HeLa cells overexpressing miR-331-3p or suppressing NRP2 revealed down-regulation of E6, E7, and p63 mRNA and up-regulation of IVL mRNA. Moreover, miR-331-3p overexpression was suppressed NRP2 expression in protein level. We showed that miR-331-3p and NRP2 were key effectors of cell proliferation by regulating the cell cycle, apoptosis. NRP-2 also regulates the expression of E6/E7 and keratinocyte differentiation markers. Our findings suggest that miR-331-3p has an important role in regulating cervical cancer cell proliferation, and that miR-331-3p may contribute to keratinocyte differentiation through NRP2 suppression. miR-331-3p and NRP2 may contribute to anti-cancer effects.

Dataset Information

MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/?-catenin axis in non-small-cell lung cancer.

Publications

MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β-catenin axis in non-small-cell lung cancer.

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