Journal Article

microRNA-30b/c inhibits non-small cell lung cancer cell proliferation by targeting Rab18

Han, Lin, Chen, Kun, Zhong, Keng, Li, Bailing

2014

Overview

Background MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptional regulate gene expression in a variety of cancers. Increasing evidences indicate that miR-30 expression is down-regulated in numerous human cancers including non-small cell lung cancer (NSCLC) which hypothesizes that miR-30 may play an important role in tumorigenesis. The aim of this study was to investigate the target gene of miR-30 and its roles in tumor growth of NSCLC. Methods Luciferase reporter assays were employed to validate regulation of a putative target of miR-30. The effect of miR-30 on endogenous levels of this target were subsequently confirmed via Western blot (WB). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-30 in NSCLC specimens and adjacent non-tumor tissues. MTT assays were conducted to explore the impact of miR-30 overexpression on the proliferation of human NSCLC cells. Results Both miR-30b and miR-30c (miR-30b/c) were found having target site in same region of Rab18 mRNA. Luciferase assays using a reporter carrying a putative miR-30b/c target site in the coding DNA sequence (CDS) region of Rab18 revealed that miR-30b/c directly targeted Rab18. Overexpression of miR-30b/c led to down-regulation of Rab18 in A549 and H23 cells at protein levels but not mRNA levels. Down-regulation of miR-30b/c and up-regulation of Rab18 protein levels were detected in NSCLC specimens compared with adjacent non-tumor tissues. Overexpression of miR-30b/c suppressed NSCLC cells growth. Knockdown of Rab18 by siRNA significantly inhibited the proliferation of NSCLC cells. Conclusions We demonstrated that miR-30b/c was down-regulated in NSCLC specimens compared with adjacent non-tumor tissues. miR-30b/c directly targeted and down-regulated Rab18 expression and inhibited NSCLC cells proliferation. These data indicated that miR-30b/c could serve as a tumor suppressor gene involved in NSCLC pathogenesis.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Base Sequence / Biomedical and Life Sciences / Biomedicine / Cancer Research / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - pathology / Cell and molecular biology / Cell growth / Cell Line, Tumor / Cell Proliferation / Gene Expression / Genes, Reporter / Health Promotion and Disease Prevention / Hospitals / Humans / Lung cancer / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Medicine/Public Health / MicroRNAs / MicroRNAs - chemistry / MicroRNAs - genetics / Oncology / Proteins / rab GTP-Binding Proteins - chemistry / rab GTP-Binding Proteins - genetics / Research Article / RNA Interference / Studies / Surgical Oncology / Tumorigenesis