TY - EJOU
AU - ZHU, DAWEI
AU - ZHANG, LEI
AU - SHI, XIAOKAI
AU - GAO, SHENGLIN
AU - YUE, CHUANG
AU - ZHANG, LIFENG
AU - BAI, YU
AU - WANG, QIFENG
AU - OKADA, ATSUSHI
AU - YASUI, TAKAHIRO
AU - WANG, CHAO
AU - CUI, XINGANG
AU - ZUO, LI
TI - RNF43 is a novel tumor-suppressor and prognostic indicator in clear cell renal cell carcinoma
T2 - Oncology Research
PY - 2021
VL - 29
IS - 3
SN - 1555-3906
AB - Identifying prognostic indicators of clear cell renal cell carcinoma (ccRCC) and elucidating the mechanisms
underlying ccRCC progression are crucial for improving ccRCC patient prognosis. This study investigated the clinical
significance and biological role of Ring finger protein 43 (RNF43) in ccRCC. Two independent cohorts of patients with
ccRCC were employed to determine the prognostic significance of RNF43 by immunohistochemistry and statistical
analyses. In vitro and in vivo experiments, RNA-seq, and other techniques were used to determine the biological role of
RNF43 in ccRCC and related molecular mechanisms. RNF43 expression was commonly decreased in ccRCC specimens,
and low expression of RNF43 indicated a higher TNM stage, SSIGN score, and WHO/ISUP grade and short survival in
patients with ccRCC. Additionally, RNF43 overexpression suppressed the proliferation, migration, and targeted drug
resistance of ccRCC cells, while the knockdown of RNF43 enhanced these characteristics of ccRCC. RNF43 knockdown
activated YAP signaling by decreasing YAP phosphorylation by p-LATS1/2 and increasing the transcription and nuclear
distribution of YAP. By contrast, RNF43 overexpression showed the opposite effects. Decreasing YAP abolished the
effect of RNF43 knockdown in promoting the malignant features of ccRCC. Additionally, restoring RNF43 expression
suppressed the resistance of the targeted drug pazopanib in in vivo orthotopic ccRCC. Furthermore, combining the
expression of RNF43 and YAP with TNM stage or the SSIGN score exhibited greater accuracy than any of these
indicators alone in assessing the postoperative prognosis of ccRCC patients. In summary, our study identified a novel
tumor suppressor, RNF43, which is also a prognostic indicator and potential target for ccRCC.
KW - Clear cell renal cell carcinoma
KW - RNF43
KW - Prognosis
KW - YAP
KW - Tumor progression
DO - 10.32604/or.2022.03458