title: KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma.
abstract: Potassium inwardly rectifying channel, subfamily J, member 1 (KCNJ1), as an ATP-dependent potassium channel, plays an essential role in potassium balance. KCNJ1 variation is associated with multiple diseases, such as antenatal Bartter syndrome and diabetes. However, the role of KCNJ1 in clear cell renal cell carcinoma (ccRCC) is still unknown. Here, we studied the expression and function of KCNJ1 in ccRCC. The expression of KCNJ1 was evaluated in ccRCC tissues and cell lines by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry analysis. The relationship between KCNJ1 expression and clinicopathological characteristics was analyzed. p3xFLAG-CMV-14 vector containing KCNJ1 was constructed and used for transfecting ccRCC cell lines 786-O and Caki-2. The effects of KCNJ1 on cell proliferation, invasion, and apoptosis were detected in ccRCC cell lines using cell proliferation assay, transwell assay, and flow cytometry, respectively. We found that KCNJ1 was low-expressed in ccRCC tissues samples and cell lines, and its expression level was significantly associated with tumor pathology grade (P = 0.002) and clinical stage (P = 0.023). Furthermore, the KCNJ1 expression was a prognostic factor of ccRCC patient's survival (P = 0.033). The re-expression of KCNJ1 in 786-O and Caki-2 significantly inhibited cancer cell growth and invasion and promoted cancer cell apoptosis. Moreover, knockdown of KCNJ1 in HK-2 cells promoted cell proliferation. Collectively, these data highlight that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis.
authors.affiliation: Department of Urology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Guo
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.forename: Boxing
authors.initials: B
authors.lastname: Su
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Xing
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.forename: Weimin
authors.initials: W
authors.lastname: Ci
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis
chemical_list: C086989:KCNJ1 protein, human; D024661:Potassium Channels, Inwardly Rectifying