KLF6及其剪切变体在肿瘤转移中的作用

鑫 张(桂林医学院基础医学院，中国)
健 黄(桂林医学院基础医学院，中国)

摘要

KLF6 是一种在人体内广泛表达的抑癌基因，参与增殖、凋亡、分化、发育和信号传导等生物学过程。但在多种肿瘤中由于杂合子缺失、体细胞突变及选择性剪切等方式失去抑癌基因的功能，并对肿瘤的发展及转移起到促进作用，论文就野生型KLF6、KLF6 剪接变异体及非编码 RNA 对肿瘤转移的作用及机制进行综述。

关键词

KLF6；剪接变异体；肿瘤转移

参考

Kim Y,Ratziu V,Choi S G, etal.Transcriptional activation of transforming growth factor beta1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1.Potential mechanisms for autocrine fibrogenesis in response to injury[J].J. Biol. Chem,1998,273.

Koritschoner N P,Bocco J L,Panzetta-Dutari G M,etal.A novel human zinc finger protein that interacts with the core promoter element of a TATA box-less gene[J].J. Biol. Chem,1997,272.

Rouby S E,Rao P H,Newcomb E W.Assignment of the Human B-Cell-Derived (BCD1) Proto-oncogene to 10p14-p15.[J].Genomics,1997(03):0-397.

Zhao J L,Austen K F,Lam B K.Cell-specific transcription of leukotriene C(4) synthase involves a Kruppel-like transcription factor and Sp1[J].J. Biol. Chem.,2000(27): 3-10.

Chiambaretta Frédéric,Blanchon Loïc,Rabier Bénédicte,etal.Regulation of corneal keratin-12 gene expression by the human Krüppel-like trans-cription factor 6 [J].Invest. Ophthalmol. Vis. Sci.,2002(43):22-9.

Kojima S,Hayashi S,Shimokado K,etal.Transcriptional activati- on of urokinase by the Krüppel-like factor Zf9/COPEB activates latent TGF-β1 in vascular endothelial cells[J].Blood,2000(95):1309-1316.

Das Amitava,Fernandez-Zapico Martin E,Cao Sheng,etal.Disruption of an SP2/KLF6 repression complex by SHP is required for farnesoid X receptor-induced endothelial cell migration[J].J. Biol. Chem.,2006(28):5-13.

Narla G, Heath K E, Reeves H L, etal. KLF6, a candidate tumor suppressor gene mutated in prostate cancer[J]. Science, 2001(29):3-6.

DiFeo Analisa, Narla Goutham, Hirshfeld Jennifer, et al. Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination[J]. Clin. Cancer Res., 2006(12): 3730-3739.

Spinola Monica, Leoni Vera P, Galvan Antonella, et al. Genome- wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene[J]. Cancer Lett., 2007(251):311-316.

Bureau Christophe, Hanoun Naima, Torrisani Jérôme, et al. Expre- ssion and Function of Kruppel Like-Factors (KLF) in Carcinogen- esis[J]. Curr. Genomics, 2009(10):353-360.

Gao Yu, Li Hongzhao, Ma Xin, etal. KLF6 Suppresses Metastasis of Clear Cell Renal Cell Carcinoma via Transcriptional Repression of E2F1[J]. Cancer Res., 2017(77):330-342.

Shin Chanseok, Manley James L. Cell signalling and the control of pre-mRNA splicing[J]. Nat. Rev. Mol. Cell Biol., 2004(05):727-738.

Narla Goutham, Difeo Analisa, Reeves Helen L, etal. A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk[J]. Cancer Res., 2005(65):1213-1222.

Pastushenko Ievgenia, Blanpain Cédric. EMT Transition States during Tumor Progression and Metastasis[J]. Trends Cell Biol., 2019(29):212-226.

Lamouille Samy, Xu Jian, Derynck Rik. Molecular mechanisms of epithelial-mesenchymal transition. [J]. Nat. Rev. Mol. Cell Biol., 2014(15):178-196.

Brabletz T, Kalluri R, Nieto M A, etal. EMT in cancer[J]. Nature reviews. Cancer, 2018(02):128-134.

Nisticò Paola, Bissell Mina J, Radisky Derek C. Epithelial-mesen- chymal transition: general principles and pathological relevance with special emphasis on the role of matrix metalloproteinases[J]. Cold Spring Harb Perspect Biol, 2012(04).

Zhang Qing, Tan Xiao-ping, Yuan Yue-sha, etal. Decreased expre- ssion of KLF6 and its significance in gastric carcinoma[J]. Med. Oncol., 2010(27):1295-1302.

Kong Ling-Min, Yao Li, Lu Ning, et al. Interaction of KLF6 and Sp1 regulates basigin-2 expression mediated proliferation, invasion and metastasis in hepatocellular carcinoma[J]. Oncotarget, 2016(07):75-87.

Wen Pei-Hao, Wang Dong-Yu, Zhang Jia-Kai, et al. Kruppel-like factor 6 suppresses growth and invasion of hepatocellular carcinoma cells in vitro and in vivo[J]. Int J Immunopathol Pharmacol, 2016(29): 666-675.

Ahronian L G, Zhu L J, Chen Y-W, et al. A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination[J]. Oncogene, 2016(35): 4653-4662.

Gao Yu, Li Hongzhao, Ma Xin etal. KLF6 Suppresses Metastasis of Clear Cell Renal Cell Carcinoma via Transcriptional Repression of E2F1. [J]. Cancer Res., 2017(77): 330-342.

Jiang Nan, Niu Gang, Pan Ying-Hua, etal. CBX4 transcriptionally suppresses KLF6 via interaction with HDAC1 to exert oncogenic activities in clear cell renal cell carcinoma[J]. EBioMedicine, 2020(53): 102-692.

Hsu Li-Sung, Huang Ren-Hung, Lai Hung-Wen, etal. KLF6 inhibited oral cancer migration and invasion via downregulation of mesenchymal markers and inhibition of MMP-9 activities[J]. Int J Med Sci, 2017(14): 530-535.

Narla Goutham, DiFeo Analisa, Yao Shen, etal. Targeted inhibiti- on of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread[J]. Cancer Res., 2005(65): 5761-5768.

Narla Goutham, DiFeo Analisa, Fernandez Yolanda, etal. KLF6- SV1 overexpression accelerates human and mouse prostate cancer progression and metastasis[J]. J. Clin. Invest., 2008(118):2711-2721.

Hatami Raheleh, Sieuwerts Anieta M, Izadmehr Sudeh, etal. KLF6-SV1 drives breast cancer metastasis and is associated with poor survival[J]. Sci Transl Med, 2013(05):169-172.

Wang Jian, Wang Xiao, Wang Yawei, etal. Krüppel like factor 6 splice variant 1 (KLF6-SV1) overexpression recruits macrophages to participate in lung cancer metastasis by up-regulating TWIST1 [J]. Cancer Biol. Ther., 2019(20):680-691.

Tejero Rut,Navarro Alfons,Campayo Marc etal. miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma[J] .PLoS ONE, 2014, 9: e101899.

Zhang Nan,Yan Qian-Qian,Lu Lu et al. The KLF6 splice variant KLF6-SV1 promotes proliferation and invasion of non-small cell lung cancer by up-regultating PI3K-AKT signaling pathway[J] .J Cancer, 2019(10):5324-5331.

Chen Hui, Chen Lili, Sun Lingyu, etal. A small interfering RNA targeting the KLF6 splice variant, KLF6-SV1, as gene therapy for gastric cancer. [J]. Gastric Cancer, 2011(14):339-352.

Anastasiadou Eleni, Jacob Leni S, Slack Frank J. Non-coding RNA networks in cancer[J]. Nat. Rev. Cancer, 2018(18):15-18.

Wang Ke, Ren Yu, Liu Yang, et al. miR-4262 Promotes Proliferat- ion and Invasion of Human Breast Cancer Cells Through Directly Targeting KLF6 and KLF15. [J]. Oncol. Res., 2017(25):277-283.

Luo Dongming, Chen Junqiang, Huang Shifeng, etal. MicroRNA- 18b acts as an oncogene in gastric cancer by directly targeting Kruppel-like factor 6[J]. Mol Med Rep, 2019(19):1926-1934.

Yang Fan, Ma Jianjun, Tang Qisheng, etal. MicroRNA-543 prom- otes the proliferation and invasion of clear cell renal cell carcinoma cells by targeting Krüppel-like factor 6[J]. Biomed. Pharmacother., 2018(97):616-623.

Han X-T, Jiang J-Q, Li M-Z, etal. Circular RNA circ-ABCB10 pr-omotes the proliferation and invasion of thyroid cancer by targeti- ng KLF6[J]. wEur Rev Med Pharmacol Sci, 2020(24):1271-1277.

Zhao Y, Qin X-P, Lang Y-P, et al. Circular RNA circ-SMAD7 pro-moted ovarian cancer cell proliferation and metastasis by suppres-sing KLF6[J]. Eur Rev Med Pharmacol Sci, 2019(23):5603-5610

Yang Haiyang, Peng Minqi, Li Yanjiao, etal. LINC00703 Acts as a Tumor Suppressor via Regulating miR-181a/KLF6 Axis in Gastric Cancer[J]. J Gastric Cancer, 2019(19):460-472.

Shi Shengli, Li Defeng, Li Yingfei, et al. LncRNA CR749391 acts as a tumor suppressor to upregulate KLF6 expression via interacting with miR-181a in gastric cancer[J]. Exp Ther Med, 2020(19):569-578.

Guo F-F,Jiang M-M,Hong L-L etal. Long non-coding RNA OR3A4 promotes metastasis of ovarian cancer via inhibiting KLF6[J]. Eur Rev Med Pharmacol Sci, 2019(23):2360-2365.

Li Y, Hou C-Z, Dong Y-L, et al. Long noncoding RNA LINP1 promoted proliferation and invasion of ovarian cancer via inhibiting KLF6[J]. Eur Rev Med Pharmacol Sci, 2020(24):36-42.

DOI: http://dx.doi.org/10.26549/yzlcyxzz.v3i3.3771