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

• Published in: World journal of surgical oncology 2015-05, Vol.13 (1), p.175-175, Article 175
• Main Authors: Peng, Jingtao, Mo, Ren, Ma, Jian, Fan, Jie
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - pharmacology; Apoptosis - drug effects; Blotting, Western; Cancer; Carcinoma, Renal cell; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cell Proliferation - drug effects; Chemotherapy; Drug Resistance, Neoplasm - genetics; Female; Fluorouracil; Fluorouracil - pharmacology; Follow-Up Studies; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Health aspects; Humans; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Male; MicroRNA; MicroRNAs - genetics; Middle Aged; Neoplasm Grading; Neoplasm Staging; Oncology, Experimental; Prognosis; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Tumor Cells, Cultured
• ISSN: 1477-7819; 1477-7819
• DOI: 10.1186/s12957-015-0596-4

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. 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. 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. 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.