MicroRNA-22 functions as a tumor suppressor by targeting SIRT1 in renal cell carcinoma.
Accumulating evidence demonstrates that microRNA-22 (miR-22) was deregulated in many types of cancers and was involved in various cellular processes related to carcinogenesis. However, the exact roles and mechanisms of miR-22 remain unknown in human renal cell carcinoma (RCC). Here, the relationship between miR-22 expression pattern and clinicopathological features of patients with EOC were determined by real-time quantitative RT-PCR (qRT-PCR). Furthermore, the role of miR-22 and possible molecular mechanisms in EOC were investigated by several in vitro approaches and in a nude mouse model. Results from qRT-PCR showed that miR-22 was significantly downregulated in RCC samples compared with corresponding non-cancerous tissues, which was significantly associated with tumor stage and lymph node metastasis. Functional study demonstrated that enforced overexpression of miR-22 in renal cancer cells inhibited proliferation, migration and invasion, and induced cell apoptosis in vitro, and suppressed tumor growth in vivo. In addition, SIRT1 was identified as a direct target of miR-22 by a luciferase reporter assay. Overexpression of miR-22 activated p53 and its downstream target p21 and PUMA, and the apoptosis markers cleaved CASP3 and PARP, and inhibited epithelial-mesenchymal transition (EMT). These findings showed that miR-22 functioned as tumor suppressor in RCC and blocked RCC growth and metastasis by directly targeting SIRT1 in RCC, indicating a potential novel therapeutic role in RCC treatment.
Internal Medicine Department, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Shoulin
S
Zhang
Scientific Research Office, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Dongmei
D
Zhang
College of Pharmacy, Changchun University of Chinese Medicine, Changchun Jingyue National High-Tech Industrial Development Zone, Changchun, Jilin 130117, P.R. China.
Chunguang
C
Yi
Internal Medicine Department, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Yinping
Y
Wang
Internal Medicine Department, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Hongan
H
Wang
Internal Medicine Department, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Jian
J
Wang
D020413:3' Untranslated Regions; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; C447939:SIRT1 protein, human; D056564:Sirtuin 1