微小RNA-513c-5p在宫颈癌中的表达及靶向组蛋白去乙酰化酶1调节宫颈癌细胞迁移和侵袭的机制

王丽娜 刘永娟 张莹 刘荣霞 梁珊 宋春红 崔娜

解剖学报 ›› 2021, Vol. 52 ›› Issue (1) : 73-77.

PDF(4562 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(4562 KB)
解剖学报 ›› 2021, Vol. 52 ›› Issue (1) : 73-77. DOI: 10.16098/j.issn.0529-1356.2021.01.011
肿瘤生物学

微小RNA-513c-5p在宫颈癌中的表达及靶向组蛋白去乙酰化酶1调节宫颈癌细胞迁移和侵袭的机制

  • 王丽娜1 刘永娟1 张莹1 刘荣霞1 梁珊1 宋春红2 崔娜3*
作者信息 +

MicroRNA-513c-5p expression in cervical cancer and targeting histone deacetylase 1 regulating cervical cancer  cell migration and invasion

  • WANG Li-na LIU Yong-juan1  ZHANG Ying1  LIU Rong-xia1  LIANG Shan SONG Chun-hong2  CUI Na3*
Author information +
文章历史 +

摘要

目的  探讨微小RNA(miR)-513c-5p在宫颈癌中的表达及靶向组蛋白去乙酰化酶1(HDAC1)调节宫颈癌细胞迁移和侵袭的机制。 方法  临床收集宫颈癌患者86例,通过Real-time PCR检测肿瘤组织和癌旁组织中miR-513c-5p水平,分析其与宫颈癌病理特征的关系。通过双荧光素酶报告验证miR-513c-5p靶向HDAC1。将宫颈癌HeLa细胞系分为4组:对照组、类似物(mimic)组、mimic+HDAC1组和HDAC1组。通过质粒转染技术过表达miR-513c-5p和(或)HDAC1。Real-time PCR和Western blotting分别用于检测RNA或蛋白的表达水平。分别通过CCK-8法、细胞划痕实验和Transwell实验检测各组的细胞生长、迁移和侵袭能力。 结果  宫颈癌组织中miR-513c-5p水平显著低于癌旁组织。低水平的miR-513c-5p与更高的局部侵袭、淋巴转移和远端转移有关(P<0.05)。miR-513-5p靶向抑制HDAC1表达。过表达miR-513c-5p显著抑制宫颈癌细胞生长、迁移和侵袭(P<0.05)。过表达HDAC1促进细胞生长、迁移和侵袭(P<0.05),并且可以逆转miR-513c-5p的抑制作用(P<0.05)。  结论  低水平的miR-513c-5p可能与宫颈癌转移有关,并且miR-513c-5p可通过靶向抑制HDAC1蛋白的表达抑制宫颈癌HeLa细胞生长、迁移和侵袭。

Abstract

Objective  To investigate the expression  of microRNA (miR)-513c-5p in cervical cancer and the mechanism  of targeting histone deacetylase 1 (HDAC1) regulating cervical cancer cell migration and invasion.   Methods  Clinically collected 86 patients with cervical cancer. The levels of miR-513c-5p in tumor tissues and adjacent tissues were detected by Real-time PCR. The relationship between miR-513c-5p and pathological characteristics of cervical cancer was analyzed. It was verified that miR-513c-5p targets HDAC1 by a dual luciferase report. Cervical cancer HeLa cells were divided into four groups: control group, mimic group, mimic+HDAC1 group and HDAC1 group. MiR-513c-5p and(or) HDAC1 were overexpressed by plasmid transfection technology. Real-time PCR and Western blotting were used to detect the expression level of RNA or protein, respectively. The cell growth, migration, and invasion capabilities of each group were measured by CCK-8 method , cell scratch test, and Transwell test.   Results  The level of miR-513c-5p in cervical cancer tissues was significantly lower than that in adjacent tissues. Low levels of miR-513c-5p were associated with higher local invasion, lymphatic metastasis, and distal metastasis (P<0.05). MiR-513-5p targeted HDAC1 expression. Overexpression of miR-513c-5p inhibited significantly the growth, migration and invasion of cervical cancer cells (P<0.05). Overexpression of HDAC1 promoted growth, migration and invasion (P<0.05), and reversed the inhibitory effect of miR-513c-5p (P<0.05).   Conclusion  Low levels of miR-513c-5p might be related to cervical cancer metastasis, and miR-513c-5p could inhibit the growth, migration and invasion of cervical cancer HeLa cells by targeted inhibition of HDAC1 protein expression.

关键词

宫颈癌 / 微小RNA-513c-5p / 组蛋白去乙酰化酶1 / 迁移 / 侵袭 / 双荧光素酶报告 / 实时定量聚合酶链反应 / 免疫印迹法 /

Key words

Cervical cancer / MicroRNA-513c-5p / Histone deacetylase 1 / Migration / Invasion / Dual luciferase report / Real-time PCR / Western blotting / Human

引用本文

导出引用
王丽娜 刘永娟 张莹 刘荣霞 梁珊 宋春红 崔娜. 微小RNA-513c-5p在宫颈癌中的表达及靶向组蛋白去乙酰化酶1调节宫颈癌细胞迁移和侵袭的机制[J]. 解剖学报. 2021, 52(1): 73-77 https://doi.org/10.16098/j.issn.0529-1356.2021.01.011
WANG Li-na LIU Yong-juan ZHANG Ying LIU Rong-xia LIANG Shan SONG Chun-hong CUI Na. MicroRNA-513c-5p expression in cervical cancer and targeting histone deacetylase 1 regulating cervical cancer  cell migration and invasion[J]. Acta Anatomica Sinica. 2021, 52(1): 73-77 https://doi.org/10.16098/j.issn.0529-1356.2021.01.011
中图分类号: R737.33   

参考文献

[1] Gu XY, Zheng RS, Sun KX, et al. Incidence and mortality of cervical cancer in China, 2014[J]. Zhonghua Zhong Liu Za Zhi, 2018, 40(4): 241-246.
[2] Kim SY, Kawaguchi T, Yan L, et al. Clinical relevance of microRNA expressions in breast cancer validated using the cancer genome atlas (TCGA)[J]. Ann Surg Oncol, 2017, 24(10): 1-7.
[3] Zhang K, Zhao Z, Yu J, et al. LncRNA FLVCR1-AS1 acts as miR-513c sponge to modulate cancer cell proliferation, migration, and invasion in hepatocellular carcinoma[J]. J Cell Biochem, 2018, 119(7): 6045-6056.
[4] Xiao L, Wan YZ, Wang B, et al. Association between expression of HDAC1 protein and HPV16/18 infection in cervical intraepithelial neoplasia and cervical squamous cell carcinoma[J]. Journal of China Medical University, 2015, 44(5):464-467. (in Chinese)
肖莉, 万义增, 王宝, 等. 宫颈上皮内瘤变及鳞癌组织中组蛋白去乙酰化酶1的表达及与HPV16/18感染的关系[J]. 中国医科大学学报, 2015, 44(5):464-467.
[5] Tomao F, Maruccio M, Preti EP, et al. Conization in early stage cervical cancer: pattern of recurrence in a 10-year single-institution experience[J]. Int J Gynecol Cancer, 2017, 27(5): 1001-1008.
[6] Kong Q, Tang Z, Xiang F, et al. Diagnostic value of serum hsa-mir-92a in patients with cervical cancer[J]. Clin Lab, 2017, 63(2): 335-337.
[7] Chen J, Jiang CC, Jin L, et al. Regulation of PD-L1: a novel role of pro-survival signaling in cancer[J]. Ann Oncol, 2015, 27(3): 615-617.
[8] Xia HL, Lv Y, Xu CW, et al. MiR-513c suppresses neuroblastoma cell migration, invasion, and proliferation through direct targeting glutaminase (GLS)[J]. Cancer Biomark, 2017, 20(4): 589-596.
[9] Dong P, Xiong Y, Yue J, et al. miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation[J]. Oncotarget, 2018, 9(33): 23253-23263.
[10] Mosakhani N, Pazzaglia, Benassi MS, et al. MicroRNA expression profiles in metastatic and non-metastatic giant cell tumor of bone[J]. Histol Histopathol, 2012, 28(5): 671-678.
[11] Qiao W, Liu H, Liu R, et al. Prognostic and clinical significance of histone deacetylase 1 expression in breast cancer: a meta-analysis[J]. Clin Chim Acta, 2018, 483(1):209-215. 
[12] Cao LL, Song X, Pei L, et al. Histone deacetylase HDAC1 expression correlates with the progression and prognosis of lung cancer: a meta-analysis[J]. Medicine, 2017, 96(31): e7663-7666.
[13] Gupta R, Bhatt LK, Momin M. Potent antitumor activity of Laccaic acid and phenethyl isothiocyanate combination in colorectal cancer via dual inhibition of DNA methyltransferase-1 and histone deacetylase-1 [J]. Toxicol Appl Pharmacol, 2019, 19(377): e114631-114633. 
[14] Lee JW, Yang DH, Park S, et al. Trichostatin A resistance is facilitated by HIF-1α acetylation in HeLa human cervical cancer cells under normoxic conditions[J]. Oncotarget, 2017, 9(2): 2035-2049.
[15] Paydar I, Velena A, Grindrod S, et al. Abstract 5855: radiosensitization of cervical cancer cells by HDAC inhibitors[J]. Cancer Res, 2017, 77(13 Suppl): 5855.

基金

河北省自然科学基金项目

PDF(4562 KB)

Accesses

Citation

Detail

段落导航
相关文章

/