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On-line Access: 2022-07-06

Received: 2021-11-15

Revision Accepted: 2022-03-21

Crosschecked: 2022-07-06

Cited: 0

Clicked: 354

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Jiabian LIAN

https://orcid.org/0000-0003-0934-6633

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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.7 P.587-596

http://doi.org/10.1631/jzus.B2100939


ZNF750 facilitates carcinogenesis via promoting the expression of long non-coding RNA CYTOR and influences pharmacotherapy response in colon adenocarcinoma


Author(s):  Lu XIA, Hexin LIN, Yanming ZHOU, Jiabian LIAN

Affiliation(s):  Xiamen Cell Therapy Research Center, the First Affiliated Hospital of Xiamen University, Xiamen 361000, China; more

Corresponding email(s):   faster_lian@xmu.edu.cn

Key Words:  Zinc Finger Protein 750, Colon adenocarcinoma, Long non coding RNA, Chemotherapy


Lu XIA, Hexin LIN, Yanming ZHOU, Jiabian LIAN. ZNF750 facilitates carcinogenesis via promoting the expression of long non-coding RNA CYTOR and influences pharmacotherapy response in colon adenocarcinoma[J]. Journal of Zhejiang University Science B, 2022, 23(7): 587-596.

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publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2100939"
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%T ZNF750 facilitates carcinogenesis via promoting the expression of long non-coding RNA CYTOR and influences pharmacotherapy response in colon adenocarcinoma
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%A Hexin LIN
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%J Journal of Zhejiang University SCIENCE B
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T1 - ZNF750 facilitates carcinogenesis via promoting the expression of long non-coding RNA CYTOR and influences pharmacotherapy response in colon adenocarcinoma
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2100939


Abstract: 
The epidermal cell differentiation regulator zinc Finger Protein 750 (ZNF750) is a transcription factor containing the Cys2His2 (C2H2) domain, the zinc finger structure of which is located at the N-terminal 25‍‍–‍46 amino acids of ZNF750. It can promote the expression of differentiation-related factors while inhibiting the expression of progenitor cell-related genes. ZNF750 is directly regulated by p63 (encoded by the TP63 gene, belonging to the TP53 superfamily). The Krüppel-like factor 4 (KLF4), repressor element-1 (RE-1)‍-silencing transcription factor (REST) corepressor 1 (RCOR1), lysine demethylase 1A (KDM1A), and C-terminal-binding protein 1/2 (CTBP1/2) chromatin regulators cooperate with ZNF750 to repress epidermal progenitor genes and activate the expression of epidermal terminal differentiation genes (Sen et al., 2012; Boxer et al., 2014). Besides, ZNF750 and the regulatory network composed of bone morphogenetic protein (BMP) signaling pathway, long non-coding RNAs (lncRNAs) (anti-differentiation non-coding RNA (ANCR) and tissue differentiation-inducing non-protein coding RNA (TINCR)), musculoaponeurotic fibrosarcoma oncogene (MAF)/MAF family B (MAFB), grainy head-like 3 (GRHL3), and positive regulatory domain zinc finger protein 1 (PRDM1) jointly promote epidermal cell differentiation (Sen et al., 2012).

锌指蛋白750通过促进长链非编码RNACYTOR表达促进结直肠癌癌变并影响药物治疗反应

夏璐1,林和新2,周彦明3,连加辨4
1厦门大学附属第一医院,厦门市细胞治疗研究中心,中国厦门,361000
2福建医科大学附属第一医院结直肠外科,中国福州,350004
3厦门大学附属第一医院胃肠肿瘤外科,中国厦门,361000
4厦门大学附属第一医院检验科,中国厦门,361000
目的:探讨锌指蛋白750在调控长链非编码RNACYTOR表达进而影响结直肠癌发生发展中的相关表型和机制及其影响药物应答和预后的潜在临床意义。
创新点:聚焦锌指蛋白750在结肠腺癌中的促癌机制,并在其对CYTOR表达的影响及锌指蛋白750-CYTOR与结肠腺癌临床相关分子病理特征和药物疗效预测方面展开研究。
方法:在分子水平,利用蛋白质免疫印迹(western blotting)、染色质免疫沉淀-定量聚合酶链反应(ChIP-qPCR)、转录组测序(RNA-seq)、逆转录-定量聚合酶链反应(RT-qPCR)等技术手段对ZNF750和CYTOR在结肠腺癌细胞系中的表达进行分析;在细胞水平,通过使用克隆形成(colony formation)、小室迁移(transwell)等方法评估ZNF750对结肠腺癌增殖、侵袭、转移功能表型的影响;在动物水平,评估在免疫缺陷的裸鼠模型中,ZNF750对人结肠腺癌细胞系皮下移植瘤生长能力的影响;对TCGA和GEO数据库中结肠腺癌患者ZNF750-CYTOR的表达量、表达相关性进行生物信息学分析,并评估在对患者预后、肿瘤免疫浸润和常规化疗药物疗效预测中的价值。
结论:锌指蛋白750正向调节CYTOR表达,且锌指蛋白750-CYTOR可促进结肠腺癌细胞的恶性表型。对TCGA或GEO结肠腺癌队列的研究结果显示,锌指蛋白750-CYTOR轴与临床特征间存在三个重要相关性:首先,锌指蛋白750-CYTOR轴在癌变和癌症进展过程上调;其次,锌指蛋白750-CYTOR与肿瘤浸润淋巴细胞(TILs)呈正相关,与免疫检查点基因的表达有关;第三,锌指蛋白750-CYTOR可作为结肠腺癌药物治疗中亚叶酸钙或奥沙利铂等常规化疗药物的反应预测因子。

关键词:锌指蛋白750;结肠腺癌;长链非编码RNACYTOR;化学药物治疗

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]BianZH, ZhangJW, LiM, et al., 2017. Long non-coding RNA LINC00152 promotes cell proliferation, metastasis, and confers 5-FU resistance in colorectal cancer by inhibiting miR-139-5p. Oncogenesis, 6(11):395.

[2]BoxerLD, BarajasB, TaoSY, et al., 2014. ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes. Genes Dev, 28(18):2013-2026.

[3]CaiJ, ZhangJ, WuP, et al., 2018. Blocking LINC00152 suppresses glioblastoma malignancy by impairing mesenchymal phenotype through the miR-612/AKT2/NF‍‍-‍‍κB pathway. J Neuro-Oncol, 140(2):225-236.

[4]CaiQ, WangZQ, WangSH, et al., 2016. Upregulation of long non-coding RNA LINC00152 by SP1 contributes to gallbladder cancer cell growth and tumor metastasis via PI3K/AKT pathway. Am J Transl Res, 8(10):‍4068-4081.

[5]CaiQ, WangZQ, WangSH, et al., 2017. Long non-coding RNA LINC00152 promotes gallbladder cancer metastasis and epithelial-mesenchymal transition by regulating HIF‍-‍‍1αvia miR-138. Open Biol, 7(1):160247.

[6]ChenPX, FangXL, XiaB, et al., 2018. Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR-125b with MCL-1 by regulating mitochondrial apoptosis pathways in ovarian cancer. Cancer Med, 7(9):4530-4541.

[7]ChenQN, ChenX, ChenZY, et al., 2017. Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression. Mol Cancer, 16:17.

[8]ChenSA, ShenX, 2020. Long noncoding RNAs: functions and mechanisms in colon cancer. Mol Cancer, 19:167.

[9]DengX, ZhaoXF, LiangXQ, et al., 2017. Linc00152 promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma. Biomed Pharmacother, 90:100-108.

[10]HaoJJ, LinDC, DinhHQ, et al., 2016. Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma. Nat Genet, 48(12):‍‍1500-1507.

[11]HazawaM, LinDC, HandralH, et al., 2017. ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma. Oncogene, 36(16):2243-2254.

[12]JiJ, TangJW, DengL, et al., 2015. LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway. Oncotarget, 6(40):42813-42824.

[13]LuchiniC, BibeauF, LigtenbergMJL, et al., 2019. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol, 30(8):1232-1243.

[14]MaP, WangHT, SunJY, et al., 2018. LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis. Cell Cycle, 17(8):974-984.

[15]OuCL, SunZQ, HeXY, et al., 2020. Targeting YAP1/LINC00152/FSCN1 signaling axis prevents the progression of colorectal cancer. Adv Sci, 7(3):1901380.

[16]PardollDM, 2012. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer, 12(4):252-264.

[17]QuJ, ZhangXQ, LvXY, 2020. Zinc finger protein 750 (ZNF750), negatively regulated by miR-17-5p, inhibits proliferation, motility and invasion of colonic cancer cells. J Gene Med, 22(8):e3195.

[18]SenGL, BoxerLD, WebsterDE, et al., 2012. ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation. Dev Cell, 22(3):669-677.

[19]ShanYQ, YingRC, JiaZ, et al., 2017. LINC00052 promotes gastric cancer cell proliferation and metastasis via activating the Wnt/β‍-catenin signaling pathway. Oncol Res, 25(9):1589-1599.

[20]ShenX, ZhongJX, YuP, et al., 2019. YY1-regulated LINC00152 promotes triple negative breast cancer progression by affecting on stability of PTEN protein. Biochem Biophys Res Commun, 509(2):448-454.

[21]SunZH, GuoX, ZangMC, et al., 2019. Long non-coding RNA LINC00152 promotes cell growth and invasion of papillary thyroid carcinoma by regulating the miR-497/BDNF axis. J Cell Physiol, 234(2):1336-1345.

[22]WangHF, ChenWX, YangP, et al., 2019. Knockdown of linc00152 inhibits the progression of gastric cancer by regulating microRNA-193b-3p/ETS1 axis. Cancer Biol Ther, 20(4):461-473.

[23]WangX, YuHF, SunWJ, et al., 2018. The long non-coding RNA CYTOR drives colorectal cancer progression by interacting with NCL and Sam68. Mol Cancer, 17:110.

[24]WangYJ, LiuJZ, BaiHZ, et al., 2017. Long intergenic non-coding RNA 00152 promotes renal cell carcinoma progression by epigenetically suppressing P16 and negatively regulates miR-205. Am J Cancer Res, 7(2):312-322.

[25]WenRH, ChenC, ZhongXH, et al., 2021. PAX6 upstream antisense RNA (PAUPAR) inhibits colorectal cancer progression through modulation of the microRNA (miR)-17-5p/zinc finger protein 750 (ZNF750) axis. Bioengineered, 12(1):3886-3899.

[26]XiaT, LiaoQ, JiangXM, et al., 2014. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep, 4:6088.

[27]XuJS, GuoJJ, JiangYK, et al., 2019. Improved characterization of the relationship between long intergenic non-coding RNA Linc00152 and the occurrence and development of malignancies. Cancer Med, 8(10):4722-4731.

[28]XuSP, WanL, YinHZ, et al., 2017. Long noncoding RNA Linc00152 functions as a tumor propellant in pan-cancer. Cell Physiol Biochem, 44(6):2476-2490.

[29]YuY, YangJ, LiQP, et al., 2017. LINC00152: a pivotal oncogenic long non-coding RNA in human cancers. Cell Prolif, 50(4):e12349.

[30]YuMJ, XueYX, ZhengJ, et al., 2017. Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway. Mol Cancer, 16:110.

[31]YueB, CaiDL, LiuCC, et al., 2016. Linc00152 functions as a competing endogenous RNA to confer oxaliplatin resistance and holds prognostic values in colon cancer. Mol Ther, 24(12):2064-2077.

[32]YueB, LiuCC, SunHM, et al., 2018. A positive feed-forward loop between LncRNA-CYTOR and Wnt/β‍-catenin signaling promotes metastasis of colon cancer. Mol Ther, 26(5):1287-1298.

[33]ZhangPP, HeQP, LeiY, et al., 2018. m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression. Cell Death Dis, 9(12):1169.

[34]ZhangYH, FuJ, ZhangZJ, et al., 2016. LncRNA-LINC00152 down-regulated by miR-376c-3p restricts viability and promotes apoptosis of colorectal cancer cells. Am J Transl Res, 8(12):5286-5297.

[35]ZhengLL, HuN, ZhouXZ, 2019. TCF3-activated LINC00152 exerts oncogenic role in osteosarcoma through regulating miR-1182/CDK14 axis. Pathol Res Pract, 215(2):373-380.

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