let-7b and let-7c are determinants of intrinsic chemoresistance in renal cell carcinoma

World Journal of Surgical Oncology

Jie Fan¹  Jian Ma¹  Ren Mo²  Jingtao Peng¹ 

[1] Department of Urology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiaotong University, 100 Haining Road, Shanghai 200080, People’s Republic of China;Department of Urology, Inner Mongolia Autonomous Region Peoples Hospital, 20 Zhaowuda Road, Hohhot 010017, Inner Mongolia, People’s Republic of China

关键词: Chemotherapy;    5-FU;    Renal cell carcinoma;    let-7c;    let-7b;    MicroRNAs;   

Others  :  1181800
DOI  :  10.1186/s12957-015-0596-4

 received in 2015-01-03, accepted in 2015-04-24,  发布年份 2015

【 摘 要 】

Background

Renal cell carcinoma (RCC) is characterized by inherent resistance to chemotherapy. Earlier studies demonstrated that microRNAs (miRNAs) might be involved in the chemosensitivity of cancers. MicroRNA let-7, a putative tumor suppressor, is dysregulated in many cancers. Our study aims to investigate the exact role of let-7 in chemotherapy sensitivity of 5-fluorouracil (5-FU) in RCC.

Methods

The clinical significance of let-7b and let-7c expression in surgically resected specimens was assessed by qRT-PCR. Cell proliferation assay and colony formation assay were used to assess the survival of 786-O cells treated with let-7b or let-7c combined with 5-FU. Western blot was used to detect the expression of Akt2 and caspase-7. Luciferase assay was used to detect the direct binding of let-7b and let-7c to the 3′-untranslated region (UTR) of Akt2.

Results

Expression of let-7b and let-7c was significantly decreased in 32 paired clear cell renal cell carcinoma tissue specimens and the dysregulation of let-7b was associated with pathological grade. Transfection of let-7b or let-7c combined with 5-FU inhibited proliferation and potentiated the antitumor efficacies of 5-FU at tolerated concentration. let-7b and let-7c suppressed the luciferase activity of reporter plasmid containing the 3′-UTR of Akt2. Overexpression of let-7b and let-7c reduced Akt2 expression, and Akt2 inhibition enhanced the sensitivity to 5-FU by affecting apoptotic pathway.

Conclusions

Expression of let-7b and let-7c was frequently decreased in clear cell renal cell carcinoma tissues. The dysregulation of let-7b and let-7c may be involved in chemoresistance of RCC cells to 5-FU by down-regulating Akt2.

【 授权许可】

   
2015 Peng et al.; licensee BioMed Central.

【 图 表 】

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