长链非编码RNA与肿瘤和干细胞

doi:10.13560/j.cnki.biotech.bull.1985.2015.07.004

摘要/Abstract

摘要： 人类基因组包含20 000多种蛋白质编码基因，只占总基因的2%左右，而90%以上的转录子是长链非编码RNA(Long non-coding RNAs，lncRNAs)。lncRNAs是广泛存在于哺乳动物基因组中的长度在200-100 000 nt之间，且不具有蛋白质编码功能的转录本。研究发现其在许多类型的肿瘤中存在异常表达，具有潜在的致癌或抑癌作用，并作为重要的调控分子参与各种生物学过程，与肿瘤的发生、发展密不可分。此外，lncRNAs在维持干细胞全能性、调控干细胞基因表达、调节干细胞自我更新和分化等方面发挥了至关重要的作用，是继microRNA后肿瘤研究的新热点。针对lncRNAs在肿瘤和干细胞生物学中的功能及相关机制作一综述，旨在为肿瘤的诊断、治疗、预后等方面提供新思路。

关键词: 长链非编码RNA, 干细胞, 肿瘤, 致癌, 抑癌, 调控

Abstract: The human genome contains more than 20 000 protein-coding genes, only approximately 2% of the total genes, while over 90% of the transcripts are long non-coding RNAs(lncRNAs). lncRNAs are transcripts commonly distributed in genomes of most mammals, with length of 200 to 100 000 nt, but not possessing function of encoding proteins. Studies have shown that lncRNAs were abnormally expressed in numerous types of cancers, playing a potential oncogenic or suppressor role in tumorigenesis. Meanwhile, lncRNAs have been found to be critical regulators of various biological processes, and they were inseparable with the occurrence and development of tumors. Besides, lncRNAs play a vital role in maintaining pluripotency and regulating the gene expression, self-regeneration and differentiation in stem cells, and they are becoming the new hot spot in cancer researches after microRNA. In this review, we summarize the functions and underlying mechanisms of lncRNAs in cancer and in stem cells biology, which aims to provide new ideas about diagnosis, treatment, and prognosis of the tumor.

Key words: long non-coding RNAs, stem cells, cancer, oncogenic, suppressor, regulate

万波, 廖世奇, 袁红霞, 马梅兰, 朱剑, 曾家豫. 长链非编码RNA与肿瘤和干细胞[J]. 生物技术通报, 2015, 31(7): 33-39.

Wan Bo, Liao Shiqi, Yuan Hongxia, Ma Meilan, Zhu Jian, Zeng Jiayu. A Review on Correlation Between Long Non-coding RNAs and Cancer as well as Stem Cells[J]. Biotechnology Bulletin, 2015, 31(7): 33-39.

参考文献

[1]Mathieu EL, Belhocine M, Dao LT, et al. Functions of lncRNA in development and diseases[J]. Medecine Sciences, 2014, 30(8-9)：790-796.
[2]Van Bakel H, Nislow C, Blencowe BJ, et al. Most “dark matter” transcripts are associated with known genes[J]. PLoS Biology, 2010, 8(5)：e1000371.
[3]Nagano T, Fraser P. No-nonsense functions for long noncoding RNAs[J]. Cell, 2011, 145：178-181.
[4]Maruyama R, Suzuki H. Long noncoding RNA involvement in cancer[J]. BMB Reports, 2012, 45(11)：604-611.
[5]Rinn JL, Kertesz M, Wang JK, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs[J]. Cell, 2007, 129(7)：1311-1323.
[6]Lin R, Maeda S, Liu C, et al. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas[J]. Oncogene, 2007, 26(6)：851-858.
[7]Ferreira LB, Palumbo A, de Mello KD, et al. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling[J]. BMC Cancer, 2012, 12：507.
[8]Wang Y, Liu XJ, Yao XD. Function of PCA3 in prostate tissue and clinical research progress on developing a PCA3 score[J]. Chinese Journal of Cancer Research, 2014, 26(4)：493-500.
[9] Hessels D, Klein Gunnewiek JM, van Oort I, et al. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer[J]. European Urology, 2003, 44(1)：8-15.
[10] Lee GL, Dobi A, Srivastava S. Prostate cancer：diagnostic performance of the PCA3 urine test[J]. Nature Reviews Urology, 2011, 8(3)：123-124.
[11]He JH, Zhang JZ, Han ZP, et al. Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells[J]. Journal of Experimental &Clinical Cancer Research, 2014, 33(1)：72.
[12]Malik R, Patel L, Prensner JR, et al. The lncRNA PCAT29 inhibits oncogenic phenotypes in prostate cancer[J]. Molecular Cancer Research, 2014, 12(8)：1081-1087.
[13]Zhu M, Sun Q, Chen Q, et al. lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI[J]. The FEBS Journal, 2014, 81(16)：3766-3775.
[14]Moore MA, Attasara P, Khuhaprema T, et al. Cancer epidemiology in mainland South-East Asia-past, present and future. [J]. Asian Pacific Journal of Cancer Prevention, 2010, 11(2)：67-80.
[15]Jemal A, Bray F, Center MM. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61：69-90.
[16]Xu TP, Huang MD, Rui X, et al. Decreased expression of the long non-coding RNA FENDRRis associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression[J]. Journal of Hematology & Oncology, 2014, 7：63.
[17]Wu Y, Zhang L, Wang Y, et al. Long noncoding RNA HOTAIR involvement in cancer[J]. Tumour Biology, 2014, 35(10)：9531-9538.
[18]Sun M, Xia R, Jin F, et al. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer[J]. Tumour Biology, 2014, 35(2)：1065-1073.
[19]Ye N, Wang B, Quan ZF, et al. Functional roles of long non-coding RNA in human breast cancer[J]. Asian Pacific Journal of Cancer Prevention, 2014, 15(15)：5993-5997.
[20]Gupta RA, Shah N, Wang KC, et al. Longnon-coding RNA HOTAR reprograms chromatin state to promote caneer metastasis[J]. Nature, 2010, 464(7291)：1071-1076.
[21]Pickard MR, Williams GT. Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells：implications for chemotherapy[J]. Breast Cancer Research and Treatment, 2014, 145(2)：359-370.
[22]Shi R, Zhou JY, Zhou H, et al. The role of PinX1 in growth control of breast cancer cells and its potential molecular mechanism by mRNA and lncRNA expression profiles screening[J]. Biomed Research International, 2014：978-984.
[23]Shi Y, Lu J, Zhou J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells[J]. Biochemical and Biophysical Research Communications, 2014, 446(2)：448-453.
[24]Ding X, Zhu L, Ji T, et al. Long Intergenic Non-Coding RNAs(LincRNAs)Identified by RNA-Seq in Breast Cancer[J]. PLoS One, 2014, 9(8)：e103270.
[25]He L, Tan X, Wang X, et al. C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion[J]. Tumour Biology, 2014, 35(12)：12181-12188.
[26]Pibouin L, Villaudy J, Ferbus D, et al. Cloning of the mRNA of overexptession in colon carcinoma-l：a sequerne overepressed in a subset of colon carcinomas[J]. Cancer Genetics and Cytogenetics, 2002, 133(1)：55-60.
[27]Ji Q, Zhang L, Liu X, et al. Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex[J]. British Journal of Cancer, 2014, 111(4)：736-748.
[28]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.
[29]Luo J, Tang L, Zhang J, et al. Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor pro-oncogenic activity in non-small cell lung cancer[J]. Tumour Biology, 2014, 35(11)：11541-11549.
[30]White NM, Cabanski CR, silva-Fisher JM, et al. Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer[J]. Genome Biology, 2014, 15(8)：429.
[31]Zhao W, An Y, Liang Y, et al. Role of HOTAIR long noncoding RNA in metastatic progression of lung cancer[J]. European Review for Medical and Pharmacological Sciences, 2014, 18(13)：1930-1936.
[32]Sun M, Liu XH, Lu KH, et al. EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition[J]. Cell Death & Disease, 2014, 5：e1298.
[33]Hou Z, Zhao W, Zhou J, et al. A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival[J]. The International Journal of Biochemistry & Cell Biology, 2014, 53：380-388.
[34]Thai P, Statt S, Chen CH, et al. Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines[J]. American Journal of Respiratory Cell and Molecular Biology, 2013, 49(2)：204-211.
[35]Peter S, Borkowska E, Drayton RM, et al. Identification of differentially expressed long non-coding RNAs in bladder cancer[J]. Clinical Cancer Research, 2014, 20(20). DOI： 10. 1158/1078-0432. CCR-14-0706.
[36]Cao W, Shi F, Wu L, et al. Genome wide screening and characterization of long non-coding RNAs in esophageal cancer[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2014, 31(5)：587-590.
[37]Xu Y, Wang J, Qiu M, et al. Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma[J]. Tumour Biology, 2014, 36(3)：1643-1651.
[38] Pan F, Yao J, Chen Y, et al. A novel long non-coding RNA FOXCUT and mRNA FOXC1 pair promote progression and predict poor prognosis in esophageal squamous cell carcinoma[J]. International Journal of Clinical and Pathology, 2014, 7(6)：2838-2849.
[39]Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals[J]. Nature, 2009, 458(7235)：223-227.
[40]Eades G, Zhang YS, Li QL, et al. Long non-coding RNAs in stem cells and cancer[J]. World Journal of Clinical Oncology, 2014, 5(2)：134-141.
[41]Sheik Mohamed J, Gaughwin PM, Lim B, et al. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells[J]. RNA, 2010, 16(2)：324-337.
[42]Guttman M, Donaghey J, Carey BW, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation[J]. Nature, 2011, 477(7364)：295-300.
[43]Huarte M, Guttman M, Feldser D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response[J]. Cell, 2010, 142(3)：409-419.
[44]Loewer S, Cabili MN, Guttman M, et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells[J]. Nature Genetics, 2010, 42(12)：1113-1117.
[45]Wang Y, Xu Z, Jiang J, et al. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal[J]. Developmental Cell, 2013, 25(1)：69-80.
[46]Zuo C, Wang Z, Lu H, et al. Expression profiling of lncRNAs in C3H10T1/2 mesenchymal stem cells undergoing early osteoblast differentiation[J]. Molecular Medicine Reports, 2013, 8(2)：463-467.
[47]Ramos AD, Diaz A, Nellore A, et al. Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo[J]. Cell Stem Cell, 2013, 12(5)：616-628.
[48]Yildirim E, Kirby JE, Brown DE, et al. Xist RNA is a potent suppressor of hematologic cancer in mice[J]. Cell, 2013, 152(4)：727-742.
[49]Kretz M, Webster DE, Flockhart RJ, et al. Suppression of progenitor differentiation requires the long noncoding RNA ANCR[J]. Genes Development, 2012, 26(4)：338-343.
[50]Sun L, Goff LA, Trapnell C, et al. Long noncoding RNAs regulate adipogenesis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(9)：3387-3392.
[51]Tang H, Wu Z, Zhang J, et al. Salivary lncRNA as a potential marker for oral squamous cell carcinoma diagnosis[J]. Molecular Medicine Reports, 2013, 7(3)761-766.