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

BMC Cancer

Keng Zhong²  Kun Chen¹  Lin Han²  Bailing Li² 

[1] Department of Respiratory Medicine, People’s Hospital of Tongren City, Guizhou 554300, China

[2] Department of Cardiothoracic Surgery, Changhai Hospital affiliated to Second Military Medical University, Shanghai 200433, China

关键词: NSCLC;    Rab18;    Proliferation;    miR-30c;    miR-30b;   

Others  :  1121038
DOI  :  10.1186/1471-2407-14-703

 received in 2014-01-15, accepted in 2014-09-17,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Zhong et al.; licensee BioMed Central Ltd.

【 图 表 】

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