Open AccessCullin 4B regulates cell survival and apoptosis in clear cell renal cell carcinoma as a target of microRNA ‐217
Author(s) -
Yang HaiFeng,
Wang ZhengLiang,
Mao TingTing,
Liu JianChang
Publication year - 2021
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12307
Subject(s) - clear cell renal cell carcinoma , gene knockdown , cancer research , cullin , apoptosis , cell growth , microrna , cell , downregulation and upregulation , medicine , biology , renal cell carcinoma , pathology , gene , biochemistry , ubiquitin ligase , ubiquitin
Cullin 4B (CUL4B) was reported to be closely related to the progression of some tumors, but its function in clear cell renal cell carcinoma (ccRCC) has not been reported. Our present study found CUL4B was upregulated in ccRCC, and CUL4B knockdown markedly inhibited ccRCC cell growth and induced apoptosis. In addition, CUL4B knockdown markedly inhibited antiapoptotic proteins' expression in ccRCC cells, including Mcl‐1 and Bcl‐2, and silenced CUL4B also induced the cleavages of PARP, an important index of apoptosis. We also confirmed microRNA‐217 (miR‐217) was downregulated in ccRCC tumor tissues, and negatively correlated with CUL4B expression. Further investigations revealed miR‐217 targeted CUL4B and markedly inhibited its expression in ccRCC cells. In addition, overexpression of miR‐217 by mimics significantly suppressed ccRCC cell growth. In contrast, enforced expression of CUL4B significantly abolished miR‐217‐induced cell survival inhibition in ccRCC cells. In conclusion, our present results suggested targeting miR‐217‐CUL4B axis would be a promising strategy for ccRCC treatment.