title: RNA-binding protein QKI-5 inhibits the proliferation of clear cell renal cell carcinoma via post-transcriptional stabilization of RASA1 mRNA.
abstract: Clear cell renal cell carcinoma (ccRCC) is a common pathological subtype of renal cancer. Although the recent application of molecular-targeted agents has modestly improved the prognosis of ccRCC patients, their outcome is still poor. It is therefore important to characterize the molecular and biological mechanisms responsible for the development of ccRCC. Approximately 25% ccRCC patients involves the loss of RNA-binding protein QKI at 6q26, but the role of QKI in ccRCC is unknown. Here, we found that QKI-5 was frequently downregulated in ccRCC patients and its down-regulation was significantly associated with clinical features including T status, M status, and differentiation grade, and poorer patient prognosis. Moreover, QKI-5 inhibited the proliferation of kidney cancer cells both in vitro and in vivo. The subsequent functional studies showed that QKI-5 stabilized RASA1 mRNA via directly binding to the QKI response element region of RASA1, which in turn prevented the activation of the Ras-MAPK signaling pathway, suppressed cellular proliferation and induced cell cycle arrest. Overall, our data demonstrate a suppressive role of QKI in ccRCC tumourigenesis that involves the QKI-mediated post-transcriptional regulation of the Ras-MAPK signaling pathway.
authors: a Cancer Center, The First Affiliated Hospital of Xinjiang Medical University , Urumqi , China.|b Key Laboratory of Infection and Cancer , Urumqi , China.
authors: Rui-Li
authors: RL
authors: Zhang
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.
authors: Jun-Ping
authors: JP
authors: Yang
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.
authors: Li-Xia
authors: LX
authors: Peng
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.
authors: Li-Sheng
authors: LS
authors: Zheng
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.
authors: Ping
authors: P
authors: Xie
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.
authors: Meng-Yao
authors: MY
authors: Wang
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.|d Department of Pathology , Sun Yat-sen University Cancer Center , Guangzhou , Guangdong , China.
authors: Yun
authors: Y
authors: Cao
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.|e Department of Urology , Sun Yat-sen University Cancer Center , Guangzhou , Guangdong , China.
authors: Zhi-Ling
authors: ZL
authors: Zhang
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.|e Department of Urology , Sun Yat-sen University Cancer Center , Guangzhou , Guangdong , China.
authors: Fang-Jian
authors: FJ
authors: Zhou
authors: c Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou , Guangdong , China.|f Department of Nasopharyngeal Carcinoma , Sun Yat-sen University Cancer Center , Guangzhou , Guangdong , China.
authors: Chao-Nan
authors: CN
authors: Qian
authors: a Cancer Center, The First Affiliated Hospital of Xinjiang Medical University , Urumqi , China.|b Key Laboratory of Infection and Cancer , Urumqi , China.
authors: Yong-Xing
authors: YX
authors: Bao
mesh_terms: D000368:Aged; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D016019:Survival Analysis; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D020729:p120 GTPase Activating Protein / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: C557248:RASA1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C000620563:RNA-binding protein QKI-5, human; D020729:p120 GTPase Activating Protein; D018631:ras Proteins
keywords: QKI-5; RASA1; Ras-MAPK signaling; ccRCC; post-transcriptional