JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2017, Vol. 55 ›› Issue (3): 94-99.doi: 10.6040/j.issn.1671-7554.0.2016.162

Previous Articles     Next Articles

Expression and role of Keap1 in renal cell carcinoma

SHI Peikun1, ZENG Beini1, WU Weifang1, HU Xiaoyan1, MA Tianjia2, ZHOU Yabin1   

  1. 1. Department of Pathogenic Biology, School of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Urology, Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Received:2016-02-22 Online:2017-03-10 Published:2017-03-10

Abstract: Objective To investigate the expression of Keap1 and evaluate its role in renal carcinoma. Methods The total RNA of tumor tissues and adjacent tissues were isolated from 32 cases of renal carcinoma treated during May 2014 to April 2015 by TRIzol. The expressions of Keap1 and NFE2L2 were detected by Q-PCR technology and immunohistochemical staining. The changes of proliferation and colony forming ability of ACHN after overexpressed Keap1 were detected by CCK-8 cell proliferation and clone formation assay. Results Q-PCR results showed that the expression of Keap1 mRNA in adjacent tissues in 75% patients was higher than that in tumor tissues(P=0.000), the expression of NFE2L2 mRNA in tumor tissues in 62% patients was higher than that in adjacent tissues(P=0.046). The immunohistochemical results showed that the expression of Keap1 protein in adjacent tissues(87.50%)was higher than that in tumor tissues(25.00%)(P=0.000), and the expression of NFE2L2 protein in tumor tissues(81.25%)was higher than that in adjacent tissues(46.88%)(P=0.004). Overexpression of Keap1 decreased proliferation and colony forming ability of renal cell carcinoma cell line ACHN. Conclusion The abnormal expression of Keap1 in tumor tissues indicates that the Keap1-NFE2L2 pathway may play an important role in renal carcinoma. Keap1 has a probable inhibiting effect on the progression of renal carcinoma.

Key words: Renal carcinoma, Kelch-like ECH-associated protein1, Proliferation, Nuclear factor E2-related factor 2

CLC Number: 

  • R574
[1] Brookman-May SD, May M, Shariat SF, et al. Time to recurrence is a significant predictor of cancer-specific survival after recurrence in patients with recurrent renal cell carcinoma-results from a comprehensive multi-centre database(CORONA/SATURN-Project)[J]. BJU Int, 2013, 112(7): 909-916.
[2] Huang Y, Li W, Su ZY, et al. The complexity of the Nrf2 pathway: beyond the antioxidant response[J]. J Nutr Biochem, 2015, 26(12): 1401-1413.
[3] OConnell MA, Hayes JD. The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic[J]. Biochem Soc Trans, 2015, 43(4): 687-689.
[4] Leinonen HM, Kansanen E, Polonen P, et al. Role of the Keap1-Nrf2 pathway in cancer[J]. Adv Cancer Res, 2014, 122: 281-320. doi: 10.1016/B978-0-12-420117-0.00008-6.
[5] Leinonen HM, Kansanen E, Polonen P, et al. Dysregulation of the Keap1-Nrf2 pathway in cancer[J]. Biochem Soc Trans, 2015, 43(4): 645-649.
[6] Kobayashi A, Kang MI, Okawa H, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2[J]. Mol Cell Biol, 2004, 24(16): 7130-7139.
[7] Guo Y, Yu S, Zhang C, et al. Epigenetic regulation of Keap1-Nrf2 signaling[J]. Free RadicBiol Med, 2015, 88(Pt B): 337-349.
[8] Rushmore TH, Morton MR, Pickett CB. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity[J]. J Biol Chem, 1991, 266(18): 11632-11639.
[9] Tian H, Zhang B, Di J, et al. Keap1: One stone kills three birds Nrf2, IKKβ and Bcl-2/Bcl-xL[J]. Cancer Letters, 2012, 325(1): 26-34.
[10] Zhao CR, Gao ZH, Qu XJ. Nrf2-ARE signaling pathway and natural products for cancer chemoprevention[J]. Cancer Epidemiol, 2010, 34(5): 523-533.
[11] Padmanabhan B, Tong KI, Ohta T, et al. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer[J]. Mol Cell, 2006, 21(5): 689-700.
[12] Wang R, An J, Ji F, et al. Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues[J]. Biochem Biophys Res Commun, 2008, 373(1): 151-154.
[13] 曹宝山, 朱翔, 陈森, 等. Keap1在非小细胞肺癌中的表达及与化疗疗效相关性的研究[J]. 中国肺癌杂志, 2012, 15(10): 591-596. CAO Baoshan, ZHU Xiang, CHEN Sen, et al. Keap1 expression for predicting the chemoresistance and prognosis of advanced non-small cell lung cancer[J]. Chinese Journal of Lung Cancer, 2012, 15(10): 591-596.
[14] 张凯茹, 闫惠琴, 王燕, 等. Nrf2及其靶基因在人肺腺癌A549顺铂耐药细胞株中的表达和意义[J]. 中国肺癌杂志, 2009, 12(11): 1150-1154. ZHANG Kairu, YAN Huiqin, WANG Yan, et al. Expression and significance of Nrf2 and its target genes in pulmonary adenocarcinoma A549 cells resistant to cisplatin[J]. Chinese Journal of Lung Cancer, 2009, 12(11): 1150-1154.
[15] Ohta T, Iijima K, Miyamoto M, et al. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth[J]. Cancer Res, 2008, 68(5): 1303-1309.
[16] Shim GS, Manandhar S, Shin DH, et al. Acquisition of doxorubicin resistance in ovarian carcinoma cells accompanies activation of the NRF2 pathway[J]. Free RadicBiol Med, 2009, 47(11): 1619-1631.
[17] Huang CF, Zhang L, Ma SR, et al. Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma[J]. PLoS One, 2013, 8(12): e83479. doi: 10.1371/journal.pone.0083479. eCollection 2013.
[1] WANG Xiao-Lei, ZHANG Hai-Thao, ZHANG Hui, GUO Cheng-Hao. Protective effects of shuxuening injecta on vascular  endothelial  cell injury in vitro due to iodine excesses [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 38-.
[2] SUN Yifeng, GAO Yu, LIANG Yongyuan, GAO Yang. Expression of CPLX2 and its in vitro effects on the proliferation migration and invasion of hepatocellular carcinoma cells [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 34-39.
[3] ZHANG Baowen, LEI Xiangli, LI Jinna, LUO Xiangjun, ZOU Rong. miR-21-5p targeted TIMP3 to inhibit proliferation and extracellular matrix accumulation of mesangial cells in Type II diabetic nephropathy mice [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 7-14.
[4] MA Qingyuan, PU Peidong, HAN Fei, WANG Chao, ZHU Zhoujun, WANG Weishan, SHI Chenhui. Effect of miR-27b-3p regulating SMAD1 on osteosarcoma cell proliferation, migration and invasion [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 32-37.
[5] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38-46.
[6] WANG Kaimin, TAN Juanjuan, YAN Zhiqiang, LI Zhiqiang. Effects of Sirtuin on hypoxia-induced proliferation of human umbilical cord-derived mesenchymal stem cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(7): 23-30.
[7] SUN Zeyu, CHEN Ying, LIN Jiaxiang, LIU Juan, ZHAO Weiming. Influence of inositol polyphosphate-4-phosphatase type II on the proliferation and apoptosis of cervical cancer cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(11): 1-6.
[8] WANG Tiantian, CHEN Jie. Expression and clinical significance of EFEMP2 in endometrial cancer tissues and cell [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 52-58.
[9] ZHAO Lu, JIAO Jun, ZHANG Teng, JIAO Xinlin, CUI Baoxia. Expression of LXRα in ovarian carcinoma and effects of T0901317 on SKOV3 cell line [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 49-53.
[10] TIAN Siqi, LIU Riqiang, YANG Ning, WEI Wei, YANG Huawei. Effect of expression of ribosomal protein S6 Kinase 4 variants on the proliferation of breast cancer cell MDA-MB-231 [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(9): 32-36.
[11] WEI Xiujuan, WU Xiuyin, TONG Dongdong, LI Jing, YANG Xiaolu, ZHANG Fenghe. Expression of BDNF/TrkB and effect of BDNF on the proliferation ability of tongue squamous cell carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(6): 50-54.
[12] ZHAO Yunxia, SONG Jing, ZHANG Cancan, LIN Xueyan, WEI Wei, TIAN Yongjie. CXXC4 promotes sensitivity to chemotherapy drugs in epithelial ovarian cancer cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(3): 24-29.
[13] TU Yunhua, KANG Yingqian, ZHOU Ying, YE Zhenyuan, XUE Yuecui, DENG Renyuan, WANG Meizhu, CHEN Lan, CAO Yu. Effect of turmeric volatile oil on the proliferation and apoptosis of human leukemia cell line THP-1 [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(5): 46-51.
[14] LIANG Yu, XIN Tao, LIU Qian, ZHENG Xiangrong, YANG Yihang, PANG Qi. Effects of theanine on the proliferation and differentiation of neural stem cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 49-54.
[15] YAO Zhong, CHEN Weiliang, XU Yangyang, HE Ying, QU Xun, LI Xingang. Galectin-9 inhibits proliferation and migration of glioma cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 1-5.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd