MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in tenal clear cell carcinoma (Cancer Cell, 2012, 21:532-546)

報告日期: 2012/10/26
報告時間: 16:00/16:50
報告學生: 朱建安
講評老師: 林秋烽
附件下載: 下載[1236-1348733749-1.pdf] 

 

VHL-Regulated MiR-204 Suppresses Tumor Growth through Inhibition of LC3B-Mediated Autophagy in Renal Clear Cell Carcinoma

Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, Drew AF, Gallo CA, Plas DR, Biesiada J, Meller J, Czyzyk-Krzeska MF. Cancer Cell 17, 532-546. (2012)

Speaker: Jian-An Ju(朱建安)                       Date: 2012/10/26 16:00-16:50

Commentator: Dr. Chiou-Feng Lin (林秋烽)                 Location: Room 602

Abstract

The clear cell renal cell carcinomas(ccRCC) is a malignant renal cancer. The von Hippel-Lindau tumor-suppressor gene (VHL) is lost in 60-80 of ccRCC. The loss of VHL can inducte the hypoxia inducible factor (HIF) to stimulate angiogenesis and to provide nutrients necessary for tumor growth [1]. Other study use antiangiogenic therapeutic to inhibit ccRCC, but it is inefficiency. This suggests that tumor growth and survival might be supported by alternative sources of nutrients such as autophagy. MicroRNAs, a small non-coding RNA, regulate cancer initiation, progression, and metastasis. MiR-204 is expressed at high level in human kidney as compared with other organs [2]. In this study, the authors investigated the role of VHL and miR-204 in the regulation of autophagic programs in ccRCC. Their results showed that miR-204 is tumor-suppressive in ccRCC and is regulated by VHL. MiR-204 is cytotoxic and inhibits macroautophagy by inhibiting LC3B-II accumulation in VHL(-/-) cells but not VHL(+/+) ccRCC cells. The authors further confirmed that LC3B is the target gene of miR-204 and autophagy is necessary for RCC tumor growth. Forthermore, VHL inducesLC3C expression by inhibiting HIF and suppresses tumor growth. Collectively, above data indicate that VHL suppresses ccRCC tumor growth by regulating autophagic programs. MiR-204 may become a ccRCC therapy tool and affects normal renal cells minimal.  

 

References

1          Gossage L, Eisen T: Alterations in vhl as potential biomarkers in renal-cell carcinoma. Nat Rev Clin Oncol 2010;7:277-288.

2          Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR: Microrna expression profiles classify human cancers. Nature 2005;435:834-838.