长链非编码RNA在宫颈癌发生、发展中作用的研究进展

doi:10.12280/gjfckx.20200425

摘要/Abstract

摘要：

宫颈癌是常见的妇科恶性肿瘤之一,其病因已较明确,主要是人乳头瘤病毒（HPV）的持续感染。近年来,随着预防疫苗问世及筛查工作的普及,宫颈癌早期诊断及早期治疗取得了一些成效,但其发生率及死亡率仍较高,严重威胁女性生命健康。积极探寻宫颈癌早期诊断和治疗方法,可进一步提高宫颈癌患者的预后。长链非编码RNA（lncRNA）是一种无蛋白质编码功能的RNA,参与多种生物学过程。lncRNA在多种恶性肿瘤中异常表达,起到致癌或抑癌的作用。越来越多的研究发现,lncRNA与宫颈癌密切相关,并在宫颈癌的发生、侵袭、转移和耐药性等方面起重要作用。探讨肺腺癌转移相关转录子1（MALAT1）、HOX反义基因间RNA（HOTAIR）、细胞周期激酶抑制因子4基因座中反义非编码RNA（ANRIL）、EBIC、CCHE1等lncRNAs在宫颈癌发生、发展中的作用,概述其在宫颈癌中的分子机制,为宫颈癌的早期诊断和靶向治疗提供新的思路。

关键词: RNA, 长链非编码, 宫颈肿瘤, 生物标记, 肿瘤, 致癌作用, 分子靶向治疗

Abstract:

Cervical cancer is one of the common gynecological malignancies. The etiology of the disease has been clear, mainly the persistent infection of human papillomavirus (HPV). In recent years, with the advent of preventive vaccines and the popularization of screening work, early diagnosis and treatment of cervical cancer have achieved some results. However, its incidence and mortality are still high, which seriously threatens the life and health of women. Actively exploring the early diagnosis and treatment of cervical cancer can further improve the prognosis of patients with cervical cancer. Long non-coding RNA (lncRNA) is a kind of RNA without protein coding function, which participates in many biological processes. lncRNA is abnormally expressed in a variety of malignant tumors and plays a role in carcinogenesis or cancer inhibition. More and more studies have found that lncRNA is closely related to cervical cancer and plays an important role in the occurrence, invasion, metastasis and drug resistance of cervical cancer. To explore the role of lncRNA such as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), HOX antisense intergenic RNA (HOTAIR), antisense non-coding RNA in the INK4 locus (ANRIL), EBIC, CCHE1 in the development of cervical cancer, and to summarize their molecular mechanisms in cervical cancer, so as to provide new ideas for the early diagnosis and targeted therapy of cervical cancer.

Key words: RNA, long noncoding, Uterine cervical neoplasms, Biomarkers, tumor, Carcinogenesis, Molecular targeted therapy

辛玉琦, 田蕾, 王晓慧. 长链非编码RNA在宫颈癌发生、发展中作用的研究进展[J]. 国际妇产科学杂志, 2021, 48(1): 41-46.

XIN Yu-qi, TIAN Lei, WANG Xiao-hui. Research Progress on the Role of Long Non-Coding RNA in the Occurrence and Development of Cervical Cancer[J]. Journal of International Obstetrics and Gynecology, 2021, 48(1): 41-46.

参考文献 40

[1]	Hu Z, Ma D. The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications[J]. Cancer Med, 2018,7(10):5217-5236. doi: 10.1002/cam4.1501. doi: 10.1002/cam4.1501 pmid: 30589505
[2]	Nakisige C, Trawin J, Mitchell-Foster S, et al. Integrated cervical cancer screening in Mayuge District Uganda (ASPIRE Mayuge): a pragmatic sequential cluster randomized trial protocol[J]. BMC Public Health, 2020,20(1):142. doi: 10.1186/s12889-020-8216-9. doi: 10.1186/s12889-020-8216-9 pmid: 32005202
[3]	Zhang L, Zhao Y, Tu Q, et al. The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy[J]. Curr Med Chem, 2020. doi: 10.2174/0929867327666200128105459. pmid: 33583367
[4]	Arredondo-Robles AV, Rodríguez-López KP, Ávila-Avilés RD. RETRACTED ARTICLE: Long non-coding RNAs in cervical cancer[J]. J Appl Genet, 2020,61(3):405. doi: 10.1007/s13353-020-00545-9. doi: 10.1007/s13353-020-00545-9 pmid: 31981186
[5]	Bin X, Hongjian Y, Xiping Z, et al. Research progresses in roles of LncRNA and its relationships with breast cancer[J]. Cancer Cell Int, 2018,18:179. doi: 10.1186/s12935-018-0674-0. doi: 10.1186/s12935-018-0674-0 pmid: 30459529
[6]	Sanchez Calle A, Kawamura Y, Yamamoto Y, et al. Emerging roles of long non-coding RNA in cancer[J]. Cancer Sci, 2018,109(7):2093-2100. doi: 10.1111/cas.13642. doi: 10.1111/cas.13642 pmid: 29774630
[7]	Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer[J]. Oncogene, 2017,36(41):5661-5667. doi: 10.1038/onc.2017.184. doi: 10.1038/onc.2017.184 pmid: 28604750
[8]	Jiang C, Yang Y, Yang Y, et al. Long Noncoding RNA (lncRNA) HOTAIR Affects Tumorigenesis and Metastasis of Non-Small Cell Lung Cancer by Upregulating miR-613[J]. Oncol Res, 2018,26(5):725-734. doi: 10.3727/096504017X15119467381615. doi: 10.3727/096504017X15119467381615 pmid: 29187267
[9]	Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis[J]. Nature, 2010,464(7291):1071-1076. doi: 10.1038/nature08975. doi: 10.1038/nature08975 pmid: 20393566
[10]	Srivastava AK, Singh PK, Rath SK, et al. Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder[J]. Tumour Biol, 2014,35(11):11435-11442. doi: 10.1007/s13277-014-2474-z. doi: 10.1007/s13277-014-2474-z pmid: 25123267
[11]	Liu J, Peng WX, Mo YY, et al. MALAT1-mediated tumorigenesis[J]. Front Biosci(Landmark Ed), 2017,22:66-80.
[12]	Prensner JR, Iyer MK, Balbin OA, et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression[J]. Nat Biotechnol, 2011,29(8):742-749. doi: 10.1038/nbt.1914. doi: 10.1038/nbt.1914 pmid: 21804560
[13]	Li ZX, Zhu QN, Zhang HB, et al. MALAT1: a potential biomarker in cancer[J]. Cancer Manag Res, 2018,10:6757-6768. doi: 10.2147/CMAR.S169406. doi: 10.2147/CMAR.S169406 pmid: 30584369
[14]	Jiang Y, Li Y, Fang S, et al. The role of MALAT1 correlates with HPV in cervical cancer[J]. Oncol Lett, 2014,7(6):2135-2141. doi: 10.3892/ol.2014.1996. doi: 10.3892/ol.2014.1996
[15]	Shen F, Zheng H, Zhou L, et al. Overexpression of MALAT1 contributes to cervical cancer progression by acting as a sponge of miR-429[J]. J Cell Physiol, 2019,234(7):11219-11226. doi: 10.1002/jcp.27772. doi: 10.1002/jcp.27772 pmid: 30515786
[16]	Zhao F, Fang T, Liu H, et al. Long non-coding RNA MALAT1 promotes cell proliferation, migration and invasion in cervical cancer by targeting miR-625-5p and AKT2[J]. Panminerva Med, 2020. doi: 10.23736/S0031-0808. doi: 10.23736/S0031-0808.21.04303-2 pmid: 33528152
[17]	Wang N, Hou MS, Zhan Y, et al. MALAT1 promotes cisplatin resistance in cervical cancer by activating the PI3K/AKT pathway[J]. Eur Rev Med Pharmacol Sci, 2018,22(22):7653-7659. doi: 10.26355/eurrev_201811_16382. doi: 10.26355/eurrev_201811_16382 pmid: 30536307
[18]	Tang Q, Hann SS. HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer[J]. Cell Physiol Biochem, 2018,47(3):893-913. doi: 10.1159/000490131. doi: 10.1159/000490131 pmid: 29843138
[19]	Liu M, Jia J, Wang X, et al. Long non-coding RNA HOTAIR promotes cervical cancer progression through regulating BCL2 via targeting miR-143-3p[J]. Cancer Biol Ther, 2018,19(5):391-399. doi: 10.1080/15384047.2018.1423921. doi: 10.1080/15384047.2018.1423921 pmid: 29336659
[20]	Zhang Y, Cheng X, Liang H, et al. Long non-coding RNA HOTAIR and STAT3 synergistically regulate the cervical cancer cell migration and invasion[J]. Chem Biol Interact, 2018,286:106-110. doi: 10.1016/j.cbi.2018.03.010. pmid: 29572071
[21]	Li Q, Feng Y, Chao X, et al. HOTAIR contributes to cell proliferation and metastasis of cervical cancer via targetting miR-23b/MAPK1 axis[J]. Biosci Rep, 2018,38(1). doi: 10.1042/BSR20171563. doi: 10.1042/BSR20171551 pmid: 29273678
[22]	Guo X, Xiao H, Guo S, et al. Long noncoding RNA HOTAIR knockdown inhibits autophagy and epithelial-mesenchymal transition through the Wnt signaling pathway in radioresistant human cervical cancer HeLa cells[J]. J Cell Physiol, 2019,234(4):3478-3489. doi: 10.1002/jcp.26828. doi: 10.1002/jcp.26828 pmid: 30367473
[23]	Kong Y, Hsieh CH, Alonso LC. ANRIL: A lncRNA at the CDKN2A/B Locus With Roles in Cancer and Metabolic Disease[J]. Front Endocrinol(Lausanne), 2018,9:405. doi: 10.3389/fendo.2018.00405.
[24]	Zhang D, Sun G, Zhang H, et al. Long non-coding RNA ANRIL indicates a poor prognosis of cervical cancer and promotes carcinogenesis via PI3K/Akt pathways[J]. Biomed Pharmacother, 2017,85:511-516. doi: 10.1016/j.biopha.2016.11.058. doi: 10.1016/j.biopha.2016.11.058 pmid: 27899255
[25]	Zhang JJ, Wang DD, Du CX, et al. Long Noncoding RNA ANRIL Promotes Cervical Cancer Development by Acting as a Sponge of miR-186[J]. Oncol Res, 2018,26(3):345-352. doi: 10.3727/096504017X14953948675449. doi: 10.3727/096504017X14953948675449 pmid: 28550682
[26]	Zhang WY, Liu YJ, He Y, et al. Down-regulation of long non-coding RNA ANRIL inhibits the proliferation, migration and invasion of cervical cancer cells[J]. Cancer Biomark, 2018,23(2):243-253. doi: 10.3233/CBM-181467. doi: 10.3233/CBM-181467 pmid: 30198868
[27]	Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view[J]. RNA Biol, 2012,9(6):703-719. doi: 10.4161/rna.20481. doi: 10.4161/rna.20481
[28]	Naemura M, Murasaki C, Inoue Y, et al. Long Noncoding RNA ANRIL Regulates Proliferation of Non-small Cell Lung Cancer and Cervical Cancer Cells[J]. Anticancer Res, 2015,35(10):5377-5382. pmid: 26408699
[29]	Sun NX, Ye C, Zhao Q, et al. Long noncoding RNA-EBIC promotes tumor cell invasion by binding to EZH2 and repressing E-cadherin in cervical cancer[J]. PLoS One, 2014,9(7):e100340. doi: 10.1371/journal.pone.0100340. doi: 10.1371/journal.pone.0100340 pmid: 25007342
[30]	Wang C, Liu X, Chen Z, et al. Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma[J]. Mol Carcinog, 2013,52(3):229-236. doi: 10.1002/mc.21848. doi: 10.1002/mc.21848 pmid: 22161744
[31]	Yang M, Zhai X, Xia B, et al. Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA[J]. Tumour Biol, 2015,36(10):7615-7622. doi: 10.1007/s13277-015-3465-4. doi: 10.1007/s13277-015-3465-4 pmid: 25921283
[32]	Chen Y, Wang CX, Sun XX, et al. Long non-coding RNA CCHE1 overexpression predicts a poor prognosis for cervical cancer[J]. Eur Rev Med Pharmacol Sci, 2017,21(3):479-483. pmid: 28239824
[33]	Qu X, Li Y, Wang L, et al. LncRNA SNHG8 accelerates proliferation and inhibits apoptosis in HPV-induced cervical cancer through recruiting EZH2 to epigenetically silence RECK expression[J]. J Cell Biochem, 2020,121(10):4120-4129. doi: 10.1002/jcb.29646. doi: 10.1002/jcb.29646 pmid: 31961005
[34]	Tian W, Lei N, Guo R, et al. Long non-coding RNA DANCR promotes cervical cancer growth via activation of the Wnt/β-catenin signaling pathway[J]. Cancer Cell Int, 2020,20:61. doi: 10.1186/s12935-020-1139-9. doi: 10.1186/s12935-020-1139-9 pmid: 32123519
[35]	Yu X, Zheng H, Chan MT, et al. HULC: an oncogenic long non-coding RNA in human cancer[J]. J Cell Mol Med, 2017,21(2):410-417. doi: 10.1111/jcmm.12956. doi: 10.1111/jcmm.12956 pmid: 27781386
[36]	Wang YF, Zhang S, Li XQ, et al. Expression of lncRNA HULC in cervical cancer and its correlation with tumor progression and patient survival[J]. Eur Rev Med Pharmacol Sci, 2016,20(19):3987-3991. pmid: 27775802
[37]	Lu W, Wan X, Tao L, et al. Long Non-Coding RNA HULC Promotes Cervical Cancer Cell Proliferation, Migration and Invasion via miR-218/TPD52 Axis[J]. Onco Targets Ther, 2020,13:1109-1118. doi: 10.2147/OTT.S232914. doi: 10.2147/OTT.S232914 pmid: 32103980
[38]	Poliseno L, Haimovic A, Christos PJ, et al. Deletion of PTENP1 pseudogene in human melanoma[J]. J Invest Dermatol, 2011,131(12):2497-2500. doi: 10.1038/jid.2011.232. doi: 10.1038/jid.2011.232 pmid: 21833010
[39]	Gao X, Qin T, Mao J, et al. PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway[J]. J Exp Clin Cancer Res, 2019,38(1):256. doi: 10.1186/s13046-019-1260-6. doi: 10.1186/s13046-019-1260-6 pmid: 31196157
[40]	Fan Y, Sheng W, Meng Y, et al. LncRNA PTENP1 inhibits cervical cancer progression by suppressing miR-106b[J]. Artif Cells Nanomed Biotechnol, 2020,48(1):393-407. doi: 10.1080/21691401.2019.1709852. doi: 10.1080/21691401.2019.1709852 pmid: 31913710