title: Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc.
abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Liu
authors.forename: Bingde
authors.initials: B
authors.lastname: Yin
authors.forename: Changcun
authors.initials: C
authors.lastname: Zhang
authors.forename: Libin
authors.initials: L
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D062085:RNA, Long Noncoding
chemical_list: C568997:MIR17HG, human; C489427:MYC protein, human; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; C487931:mirnlet7 microRNA, human; D019938:Cyclin D1