长链非编码RNA在宫颈癌中的作用

doi:10.12280/gjfckx.20211109

摘要/Abstract

摘要：

宫颈癌是女性最常见的恶性肿瘤之一,我国的发病率和死亡率一直居高不下。人乳头瘤病毒的持续感染是宫颈癌的主要危险因素,但并非唯一因素,遗传和表观遗传因素与宫颈癌的关系不容忽视。近年有研究发现长链非编码RNA（long non-coding RNA,lncRNA）与宫颈癌的发生、发展有关。许多lncRNA可以作为竞争性内源RNA（competing endogenous RNA,ceRNA）广泛参与调控一些关键的信号通路,如Wnt/β-catenin依赖性途径、丝裂原活化蛋白激酶通路、磷脂酰肌醇3激酶/蛋白激酶B通路和Notch信号通路等,从而在宫颈癌的发生、发展中发挥致癌或抑癌作用,因此许多lncRNA已成为宫颈癌新的诊断和预后生物标志物。综述lncRNA的结构与功能,以及lncRNA在宫颈癌中的作用机制。

关键词: 宫颈肿瘤, RNA,长链非编码, 竞争性内源RNA, 信号传导, 基因

Abstract:

Cervical cancer is one of the most common malignancies in women. The morbidity and mortality in China remain high. Persistent infection with human papillomavirus (HPV) is a main risk factor for cervical cancer, but it is not the only factor. The relationship between genetic and epigenetic factors and cervical cancer can not be ignored. In recent years, studies have found that long non-coding RNAs (lncRNAs) are related to the occurrence and development of cervical cancer. Many lncRNAs can be widely involved in the regulation of some key signal pathways as competing endogenous RNA (ceRNA), such as Wnt/β-catenin dependent pathway, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), Notch signaling pathway. LncRNAs play an important role in carcinogenesis or tumor inhibition in the occurrence and development of cervical cancer, so that many lncRNAs have become new diagnostic and prognostic biomarkers of cervical cancer. Therefore, this paper reviews the structure and function of lncRNA and the mechanism of lncRNA in cervical cancer.

Key words: Uterine cervical neoplasms, RNA, long noncoding, Competitive endogenous RNA, Signaling transduction, Genes

李琦, 赵卫红. 长链非编码RNA在宫颈癌中的作用[J]. 国际妇产科学杂志, 2022, 49(4): 388-392.

LI Qi, ZHAO Wei-hong. The Role of LncRNA in Cervical Cancer[J]. Journal of International Obstetrics and Gynecology, 2022, 49(4): 388-392.

参考文献 44

[1]	Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics,2020:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin,2021, 71(3):209-249. doi: 10.3322/caac.21660. doi: 10.3322/caac.21660
[2]	Della Fera AN, Warburton A, Coursey TL, et al. Persistent Human Papillomavirus Infection[J]. Viruses, 2021, 13(2):321. doi: 10.3390/v13020321. doi: 10.3390/v13020321
[3]	Yeo-Teh NSL, Ito Y, Jha S. High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis[J]. Int J Mol Sci, 2018, 19(6):1706. doi: 10.3390/ijms19061706. doi: 10.3390/ijms19061706
[4]	Sharma S, Munger K. The Role of Long Noncoding RNAs in Human Papillomavirus-associated Pathogenesis[J]. Pathogens, 2020, 9(4):289. doi: 10.3390/pathogens9040289. doi: 10.3390/pathogens9040289
[5]	Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?[J]. Cell, 2011, 146(3):353-358. doi: 10.1016/j.cell.2011.07.014. doi: 10.1016/j.cell.2011.07.014
[6]	Chan JJ, Tay Y. Noncoding RNA: RNA Regulatory Networks in Cancer[J]. Int J Mol Sci, 2018, 19(5):1310. doi: 10.3390/ijms19051310. doi: 10.3390/ijms19051310
[7]	Chu Q, Gu X, Zheng Q, et al. Long noncoding RNA SNHG4: a novel target in human diseases[J]. Cancer Cell Int, 2021, 21(1):583. doi: 10.1186/s12935-021-02292-1. doi: 10.1186/s12935-021-02292-1
[8]	Bhan A, Soleimani M, Mandal SS. Long Noncoding RNA and Cancer: A New Paradigm[J]. Cancer Res, 2017, 77(15):3965-3981. doi: 10.1158/0008-5472.CAN-16-2634. doi: 10.1158/0008-5472.CAN-16-2634
[9]	Kim HJ, Lee DW, Yim GW, et al. Long non-coding RNA HOTAIR is associated with human cervical cancer progression[J]. Int J Oncol, 2015, 46(2):521-530. doi: 10.3892/ijo.2014.2758. doi: 10.3892/ijo.2014.2758
[10]	Liguori G, Cerrone M, De Chiara A, et al. The Role of lncRNAs in Rare Tumors with a Focus on HOX Transcript Antisense RNA (HOTAIR)[J]. Int J Mol Sci, 2021, 22(18):10160. doi: 10.3390/ijms221810160. doi: 10.3390/ijms221810160
[11]	Salmerón-Bárcenas EG, Illades-Aguiar B, Del Moral-Hernández O, et al. HOTAIR Knockdown Decreased the Activity Wnt/β-Catenin Signaling Pathway and Increased the mRNA Levels of Its Negative Regulators in Hela Cells[J]. Cell Physiol Biochem, 2019, 53(6):948-960. doi: 10.33594/000000188. doi: 10.33594/000000188 pmid: 31820855
[12]	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
[13]	Zhou Y, Wang Y, Lin M, et al. LncRNA HOTAIR promotes proliferation and inhibits apoptosis by sponging miR-214-3p in HPV16 positive cervical cancer cells[J]. Cancer Cell Int, 2021, 21(1):400. doi: 10.1186/s12935-021-02103-7. doi: 10.1186/s12935-021-02103-7 pmid: 34320988
[14]	Zhang W, Liu J, Wu Q, et al. HOTAIR Contributes to Stemness Acquisition of Cervical Cancer through Regulating miR-203 Interaction with ZEB1 on Epithelial-Mesenchymal Transition[J]. J Oncol, 2021, 2021:4190764. doi: 10.1155/2021/4190764. doi: 10.1155/2021/4190764
[15]	Botti G, Collina F, Scognamiglio G, et al. LncRNA HOTAIR Polymorphisms Association with Cancer Susceptibility in Different Tumor Types[J]. Curr Drug Targets, 2018, 19(10):1220-1226. doi: 10.2174/1389450118666170622091940. doi: 10.2174/1389450118666170622091940
[16]	Zhou YH, Cui YH, Wang T, et al. Long non-coding RNA HOTAIR in cervical cancer:Molecular marker,mechanistic insight,and therapeutic target[J]. Adv Clin Chem, 2020, 97:117-140. doi: 10.1016/bs.acc.2019.12.004. doi: 10.1016/bs.acc.2019.12.004
[17]	Shen H, Wang L, Xiong J, et al. Long non-coding RNA CCAT1 promotes cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis[J]. Cell Cycle, 2019, 18(10):1110-1121. doi: 10.1080/15384101.2019.1609829. doi: 10.1080/15384101.2019.1609829 pmid: 31084453
[18]	Li R, Liu J, Qi J. Knockdown of long non-coding RNA CCAT1 suppresses proliferation and EMT of human cervical cancer cell lines by down-regulating Runx2[J]. Exp Mol Pathol, 2020, 113:104380. doi: 10.1016/j.yexmp.2020.104380. doi: 10.1016/j.yexmp.2020.104380
[19]	Zhang L, Guo C, Ji T, et al. SOX2 Regulates lncRNA CCAT1/MicroRNA-185-3p/FOXP3 Axis to Affect the Proliferation and Self-Renewal of Cervical Cancer Stem Cells[J]. Nanoscale Res Lett, 2021, 16(1):2. doi: 10.1186/s11671-020-03449-z. doi: 10.1186/s11671-020-03449-z pmid: 33394184
[20]	Chang QQ, Chen CY, Chen Z, et al. LncRNA PVT1 promotes proliferation and invasion through enhancing Smad3 expression by sponging miR-140-5p in cervical cancer[J]. Radiol Oncol, 2019, 53(4):443-452. doi: 10.2478/raon-2019-0048. doi: 10.2478/raon-2019-0048
[21]	Liu X, Shen X, Zhang J. Long non-coding RNA LINC00514 promotes the proliferation and invasion through the miR-708-5p/HOXB3 axis in cervical squamous cell carcinoma[J]. Environ Toxicol, 2022, 37(1):161-170. doi: 10.1002/tox.23387. doi: 10.1002/tox.23387
[22]	An M, Xing X, Chen T. Long non-coding RNA UCA1 enhances cervical cancer cell proliferation and invasion by regulating microRNA-299-3p expression[J]. Oncol Lett, 2021, 22(5):772. doi: 10.3892/ol.2021.13033. doi: 10.3892/ol.2021.13033
[23]	Li L, Ma Y, Maerkeya K, et al. LncRNA OIP5-AS1 Regulates the Warburg Effect Through miR-124-5p/IDH2/HIF-1α Pathway in Cervical Cancer[J]. Front Cell Dev Biol, 2021, 9:655018. doi: 10.3389/fcell.2021.655018. doi: 10.3389/fcell.2021.655018
[24]	Zhang J, Liu HL, Liu JB, et al. LncRNA AL592284.1 facilitates proliferation and metastasis of cervical cancer cells via miR-30a-5p/Vimentin/EMT axis[J]. Biochem Biophys Res Commun, 2021, 577:95-102. doi: 10.1016/j.bbrc.2021.09.014. doi: 10.1016/j.bbrc.2021.09.014
[25]	Song H, Liu Y, Liang H, et al. SPINT1-AS1 Drives Cervical Cancer Progression via Repressing miR-214 Biogenesis[J]. Front Cell Dev Biol, 2021, 9:691140. doi: 10.3389/fcell.2021.691140. doi: 10.3389/fcell.2021.691140
[26]	Pan X, Cao YM, Liu JH, et al. MEG3 Induces Cervical Carcinoma Cells’ Apoptosis Through Endoplasmic Reticulum Stress by miR-7-5p/STC1 Axis[J]. Cancer Biother Radiopharm, 2021, 36(6):501-510. doi: 10.1089/cbr.2019.3344. doi: 10.1089/cbr.2019.3344
[27]	Zhang J, Gao Y. Long non-coding RNA MEG3 inhibits cervical cancer cell growth by promoting degradation of P-STAT3 protein via ubiquitination[J]. Cancer Cell Int, 2019, 19:175. doi: 10.1186/s12935-019-0893-z. doi: 10.1186/s12935-019-0893-z pmid: 31320837
[28]	Yang W, Xu X, Hong L, et al. Upregulation of lncRNA GAS5 inhibits the growth and metastasis of cervical cancer cells[J]. J Cell Physiol, 2019, 234(12):23571-23580. doi: 10.1002/jcp.28926. doi: 10.1002/jcp.28926
[29]	Li Y, Wan YP, Bai Y. Correlation between long strand non-coding RNA GASS expression and prognosis of cervical cancer patients[J]. Eur Rev Med Pharmacol Sci, 2018, 22(4):943-949. doi: 10.26355/eurrev_201802_14375. doi: 10.26355/eurrev_201802_14375
[30]	Zhang Y, Zhang J, Mao L, et al. Long noncoding RNA HCG11 inhibited growth and invasion in cervical cancer by sponging miR-942-5p and targeting GFI1[J]. Cancer Med, 2020, 9(19):7062-7071. doi: 10.1002/cam4.3203. doi: 10.1002/cam4.3203
[31]	Ying Y, Tao Q. Epigenetic disruption of the WNT/beta-catenin signaling pathway in human cancers[J]. Epigenetics, 2009, 4(5):307-312. doi: 10.4161/epi.4.5.9371. doi: 10.4161/epi.4.5.9371 pmid: 19633433
[32]	Wu W, Guo L, Liang Z, et al. Lnc-SNHG16/miR-128 axis modulates malignant phenotype through WNT/β-catenin pathway in cervical cancer cells[J]. J Cancer, 2020, 11(8):2201-2212. doi: 10.7150/jca.40319. doi: 10.7150/jca.40319 pmid: 32127947
[33]	Dillon M, Lopez A, Lin E, et al. Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers[J]. Cancers(Basel), 2021, 13(20):5059. doi: 10.3390/cancers13205059. doi: 10.3390/cancers13205059
[34]	Chu D, Liu T, Yao Y, et al. LINC00997/MicroRNA 574-3p/CUL2 Promotes Cervical Cancer Development via Mitogen-Activated Protein Kinase Signaling[J]. Mol Cell Biol, 2021, 41(8):e0005921. doi: 10.1128/MCB.00059-21. doi: 10.1128/MCB.00059-21
[35]	Liu X, Yang Q, Yan J, et al. LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating MAPK pathway[J]. J Cell Biochem, 2019, 120(3):4268-4277. doi: 10.1002/jcb.27712. doi: 10.1002/jcb.27712
[36]	Meng XJ, Wang JC, Wang AQ, et al. Downregulation of lncRNA CCHE1 inhibits cell proliferation, migration and invasion by suppressing MEK/ERK/c-MYC pathway in nasopharyngeal carcinoma[J]. Eur Rev Med Pharmacol Sci, 2020, 24(17):8880-8888. doi: 10.26355/eurrev_202009_22828. doi: 10.26355/eurrev_202009_22828
[37]	Martini M, De Santis MC, Braccini L, et al. PI3K/AKT signaling pathway and cancer: an updated review[J]. Ann Med, 2014, 46(6):372-383. doi: 10.3109/07853890.2014.912836. doi: 10.3109/07853890.2014.912836 pmid: 24897931
[38]	Yan SP, Chu DX, Qiu HF, et al. LncRNA LINC01305 silencing inhibits cell epithelial-mesenchymal transition in cervical cancer by inhibiting TNXB-mediated PI3K/Akt signalling pathway[J]. J Cell Mol Med, 2019, 23(4):2656-2666. doi: 10.1111/jcmm.14161. doi: 10.1111/jcmm.14161
[39]	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
[40]	Brzozowa-Zasada M, Piecuch A, Dittfeld A, et al. Notch signalling pathway as an oncogenic factor involved in cancer development[J]. Contemp Oncol(Pozn), 2016, 20(4):267-272. doi: 10.5114/wo.2016.61845. doi: 10.5114/wo.2016.61845
[41]	Rodrigues C, Joy LR, Sachithanandan SP, et al. Notch signalling in cervical cancer[J]. Exp Cell Res, 2019, 385(2):111682. doi: 10.1016/j.yexcr.2019.111682. doi: 10.1016/j.yexcr.2019.111682
[42]	Chen Y, Wu Q, Lin J, et al. DARS-AS1 accelerates the proliferation of cervical cancer cells via miR-628-5p/JAG1 axis to activate Notch pathway[J]. Cancer Cell Int, 2020, 20(1):535. doi: 10.1186/s12935-020-01592-2. doi: 10.1186/s12935-020-01592-2
[43]	He M, Wang Y, Cai J, et al. LncRNA DLEU2 promotes cervical cancer cell proliferation by regulating cell cycle and NOTCH pathway[J]. Exp Cell Res, 2021, 402(1):112551. doi: 10.1016/j.yexcr.2021.112551. doi: 10.1016/j.yexcr.2021.112551
[44]	Wu Q, Lu S, Zhang L, et al. LncRNA HOXA-AS2 Activates the Notch Pathway to Promote Cervical Cancer Cell Proliferation and Migration[J]. Reprod Sci, 2021, 28(10):3000-3009. doi: 10.1007/s43032-021-00626-y. doi: 10.1007/s43032-021-00626-y