lncRNA linc-UBC1在恶性肿瘤发生发展中的作用研究进展

doi:10.20223/j.cnki.1000-8535.2025.03.005

摘要/Abstract

摘要： 长链非编码RNA（lncRNA）是一类长度大于200个核苷酸转录本,通过调控DNA、RNA及蛋白质的表达和功能,参与肿瘤发生、发展并发挥重要作用的RNA,近年来lncRNA成为恶性肿瘤早期诊断和预后标志物研究新的关注方向。Linc-UBC1作为一种新发现的lncRNA,在多种恶性肿瘤如肺癌、胃癌、结直肠癌、宫颈癌、卵巢癌、食管鳞癌等中异常高表达,可通过作为竞争性RNA（ceRNA）、参与信号通路等促进肿瘤细胞的增殖、迁移、侵袭、细胞周期进展、细胞凋亡和上皮间充质转化（EMT）等过程;高表达的linc-UBC1能够增加恶性肿瘤的耐药性,其表达水平与肿瘤分期、淋巴结转移和原发肿瘤远处转移呈正相关;linc-UBC1有望成为许多恶性肿瘤的新型的生物标志物、预后预测因子和治疗靶点,但其具体的调控机制仍处于研究的早期阶段,有待进一步深入研究。文章就目前linc-UBC1在恶性肿瘤发生和发展中的作用研究进展进行综述。

关键词: 长链非编码RNA, linc-UBC1, 恶性肿瘤, 调控机制

Abstract: Long non-coding RNA（lncRNA）is a class of transcripts with a length of more than 200 nucleotides．It is involved in the occurrence and development of tumors and plays an important role by regulating the expression and function of DNA,RNA and protein．In recent years,lncRNA has become a new research direction for early diagnosis and prognosis of malignant tumors．As a newly discovered lncRNA,linc-UBC1 is abnormally highly expressed in a variety of malignant tumors such as lung cancer,gastric cancer,colorectal cancer,cervical cancer,ovarian cancer,and esophageal squamous cell carcinoma．It can promote the proliferation,migration,invasion,cell cycle progression,cell apoptosis and EMT of tumor cells by acting as a competing endogenous RNA（ceRNA）and participating in signaling pathways．High expression of linc-UBC1 can increase the drug resistance of malignant tumors,and its expression level is positively correlated with tumor stage,lymph node metastasis and distant metastasis of primary tumors．linc-UBC1 is expected to become a new biomarker,prognostic predictor and therapeutic target for many malignant tumors,while its specific regulatory mechanism is still in the early stage of research and needs further in-depth study．This article reviews the current research progress of linc-UBC1 in the occurrence and development of malignant tumors．

Key words: long non-coding RNA, linc-UBC1, malignant tumor, mechanisms of regulation

娄焕英, 范晓宇, 季莹莹, 王凤, 李毅, 冯强. lncRNA linc-UBC1在恶性肿瘤发生发展中的作用研究进展[J]. 广州医药, 2025, 56(3): 323-329.

LOU Huanying, FAN Xiaoyu, JI Yingying, WANG Feng, LI Yi, FENG Qiang. Research progress of long non-coding RNA linc-UBC1 in the development of malignant tumors[J]. Guangzhou Medical Journal, 2025, 56(3): 323-329.

参考文献

[1] BRIDGES M C,DAULAGALA A C,KOURTIDIS A.LNCcation:lncRNA localization and function[J].J Cell Biol,2021,220(2):e202009045.
[2] ZHANG X,XIE H,LUO M,et al.A systematic review and meta-analysis of long noncoding RNA linc-UBC1 expression and prognosis and clinicopathological phenotypes in human cancers[J].Artif Cells Nanomed Biotechnol,2020,48(1):875-884.
[3] 赵二勇,陈悦霖,易莉莎,等.LINC02038与子宫内膜癌发生、发展的关联性分析[J].广州医药,2024,55(1):18-24.
[4] CHEN X,DAI M,ZHU H,et al.Evaluation on the diagnostic and prognostic values of long non-coding RNA BLACAT1 in common types of human cancer[J].Mol Cancer,2017,16(1):160.
[5] XU R,CAO X R,ZHANG B Q,et al.BLACAT1 is negatively associated with prognosis in patients with NSCLC and inhibits cell progression,metastasis and epithelial-mesenchymal transition through down-regulating Wnt/β-catenin signaling pathway[J].Eur Rev Med Pharmacol Sci,2019,23(14):6217-6225.
[6] YAN X,ZHANG N,WANG G,et al.The prognostic significance of LncRNA BLACAT1 overexpression in various tumors:a meta-analysis[J].Front Genet,2024(15):1362420.
[7] HAN W,YU F,GUAN W.Oncogenic roles of lncRNA BLACAT1 and its related mechanisms in human cancers[J].Biomed Pharmacother,2020(130):110632.
[8] WU T,WANG Q,DING M,et al.Prognostic and clinicopathological significance of long non-coding RNA BLACAT1 in cancer:An updated meta-analysis and TCGA data review[J].Clin Lab,2020,66(11).
[9] EL SHARKAWI F Z,EL SABAH M,ATYA H B,et al.Urinary BLACAT1 as a non-invasive biomarker for bladder cancer[J].Mol Biol Rep,2023,50(5):4339-4345.
[10] SUN J,JIA J,YUAN W,et al.LncRNA BLACAT1 accelerates non-small cell lung cancer through up-regulating the activation of sonic hedgehog pathway[J].Front Oncol,2021(11):625253.
[11] HERMAN A B,TSITSIPATIS D,GOROSPE M.Integrated lncRNA function upon genomic and epigenomic regulation[J]. Mol Cell,2022,82(12):2252-2266.
[12] WANG L,MA Q,YAO R,et al.Current status and development of anti-PD-1/PD-L1 immunotherapy for lung cancer[J].Int Immunopharmacol,2020(79):106088.
[13] YOUSEFI M,GHAFFARI P,NOSRATI R,et al.Prognostic and therapeutic significance of circulating tumor cells in patients with lung cancer[J]. Cell Oncol(Dordr),2020,43(1):31-49.
[14] BODOR JN,BOUMBER Y,BORGHAEI H.Biomarkers for immune checkpoint inhibition in non-small cell lung cancer(NSCLC)[J]. Cancer,2020,126(2):260-270.
[15] YE J R,LIU L,ZHENG F.Long noncoding RNA bladder cancer associated transcript 1 promotes the proliferation,migration,and invasion of nonsmall cell lung cancer through sponging miR-144[J].DNA Cell Biol,2017,36(10):845-852.
[16] SHU D,XU Y,CHEN W.Knockdown of lncRNA BLACAT1 reverses the resistance of afatinib to non-small cell lung cancer via modulating STAT3 signalling[J].J Drug Target,2020,28(3):300-306.
[17] HUANG F X,CHEN H J,ZHENG F X,et al.LncRNA BLACAT1 is involved in chemoresistance of non-small cell lung cancer cells by regulating autophagy[J].Int J Oncol,2019,54(1):339-347.
[18] KIM S T,CRISTESCU R,BASS A J,et al.Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer[J].Nat Med,2018,24(9):1449-1458.
[19] RAJA U M,GOPAL G,SHIRLEY S,et al.Immunohistochemical expression and localization of cytokines/chemokines/growth factors in gastric cancer[J].Cytokine,2017(89):82-90.
[20] ZHU X,CAO Y,LU P,et al.Evaluation of platelet indices as diagnostic biomarkers for colorectal cancer[J].Sci Rep,2018,8(1):11814.
[21] WANG Z,LIU X,LIU X,et al.Long non-coding RNA BLACAT1 promotes the tumorigenesis of gastric cancer by sponging microRNA-149-5p and targeting KIF2A[J].Cancer Manag Res,2020(12):6629-6640.
[22] HU Y,PAN J,WANG Y,et al.Long noncoding RNA linc-UBC1 is negative prognostic factor and exhibits tumor pro-oncogenic activity in gastric cancer[J].Int J Clin Exp Pathol,2015,8(1):594-600.
[23] CHEN R,ZHOU S,CHEN J,et al.LncRNA BLACAT1/miR-519d-3p/CREB1 axis mediates proliferation,apoptosis,migration,invasion,and drug-resistance in colorectal cancer progression[J].Cancer Manag Res,2020(12):13137-13148.
[24] LULLI M,NAPOLI C,LANDINI I,et al.Role of non-coding RNAs in colorectal cancer:Focus on long non-coding RNAs[J].Int J Mol Sci,2022,23(21):13431.
[25] SU J,ZHANG E,HAN L,et al.Long noncoding RNA BLACAT1 indicates a poor prognosis of colorectal cancer and affects cell proliferation by epigenetically silencing of p15[J].Cell Death Dis,2017,8(3):e2665.
[26] CHUNG H C,ROS W,DELORD J P,et al.Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer:results from the phase II KEYNOTE-158 study[J].J Clin Oncol,2019,37(17):1470-1478.
[27] ASWATHY R,SUMATHI S.Defining new biomarkers for overcoming therapeutical resistance in cervical cancer using lncRNA[J].Mol Biol Rep,2023,50(12):10445-10460.
[28] LIU N,HU G,WANG H,et al.LncRNA BLACAT1 regulates VASP expression via binding to miR-605-3p and promotes giloma development[J].J Cell Physiol,2019,234(12):22144-22152.
[29] CHENG H,TIAN J,WANG C,et al.LncRNA BLACAT1 is upregulated in cervical squamous cell carcinoma(CSCC)and predicts poor survival[J].Reprod Sci,2020,27(2):585-591.
[30] WANG C H,LI Y H,TIAN H L,et al.Long non-coding RNA BLACAT1 promotes cell proliferation,migration and invasion in cervical cancer through activation of Wnt/β-catenin signaling pathway[J].Eur Rev Med Pharmacol Sci,2018,22(10):3002-3009.
[31] LIU H,ZENG S Y,XIE Y,et al.Linc-UBC1 stimulates the metastasis and progression of ovarian cancer via downregulating p53 level[J].Eur Rev Med Pharmacol Sci,2020,24(3):1054-1061.
[32] YANG H,QI Y,WANG X L,et al.Down-regulation of lncRNA BLACAT1 inhibits ovarian cancer progression by suppressing the Wnt/β-catenin signaling pathway via regulating miR-519d-3p[J].Mol Cell Biochem,2020,467(1-2):95-105.
[33] SUN W,SHEN NM,FU SL.Involvement of lncRNA-mediated signaling pathway in the development of cervical cancer[J].Eur Rev Med Pharmacol Sci,2019,23(9):3672-3687.
[34] LIU Y,HAO H,KANG L,et al.Construction of a novel necroptosis-related lncRNA signature for prognosis prediction in esophageal cancer[J].BMC Gastroenterol,2022,22(1):345.
[35] NIU G,ZHUANG H,LI B,et al.Long noncoding RNA linc-UBC1 promotes tumor invasion and metastasis by regulating EZH2 and repressing E-cadherin in esophageal squamous cell carcinoma[J].J BUON,2018,23(1):157-162.
[36] LOU W,DING B,FU P.Pseudogene-derived lncRNAs and their miRNA sponging mechanism in human cancer[J].Front Cell Dev Biol,2020(8):85.
[37] DAI D,FENG X D,ZHU W Q,et al.LncRNA BLACAT1 regulates the viability,migration and invasion of oral squamous cell carcinoma cells by targeting miR-142-5p[J].Eur Rev Med Pharmacol Sci,2019,23(23):10313-10323.
[38] PENG Y,LENG W,DUAN S,HONG M.Long noncoding RNA BLACAT1 is overexpressed in hepatocellular carcinoma and its downregulation suppressed cancer cell development through endogenously competing against hsa-miR-485-5p[J].Biomed Pharmacother,2019(116):109027.
[39] YUAN S,TAO F,ZHANG X,et al.Role of Wnt/β-Catenin signaling in the chemoresistance modulation of colorectal cancer[J].Biomed Res Int,2020(2020):9390878.
[40] MA J H,QIN L,LI X.Role of STAT3 signaling pathway in breast cancer[J].Cell Commun Signal,2020,18(1):33.
[41] LANTUEJOUL S,SOUND-TSAO M,COOPER WA,et al.PD-L1 testing for lung cancer in 2019:perspective from the IASLC pathology committee[J].J Thorac Oncol,2020,15(4):499-519.
[42] AALIJAHAN H,GHORBIAN S.Long non-coding RNAs and cervical cancer[J].Exp Mol Pathol,2019(106):7-16.
[43] GOU C,HAN P,LI J,et al.Knockdown of lncRNA BLACAT1 enhances radiosensitivity of head and neck squamous cell carcinoma cells by regulating PSEN1[J].Br J Radiol,2020,93(1108):20190154.
[44] WU X,GARDASHOVA G,LAN L,et al.Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis[J].Commun Biol,2020,3(1):193.
[45] LIU D,ERTAY A,HILL C,et al.ASPP1 deficiency promotes epithelial-mesenchymal transition,invasion and metastasis in colorectal cancer[J].Cell Death Dis,2020,11(4):224.
[46] JIANG M C,NI J J,CUI W Y,et al.Emerging roles of lncRNA in cancer and therapeutic opportunities[J].Am J Cancer Res,2019,9(7):1354-1366.
[47] YU Y,KOU D,LIU B,et al.LncRNA MEG3 contributes to drug resistance in acute myeloid leukemia by positively regulating ALG9 through sponging miR-155[J].Int J Lab Hematol,2020,42(4):464-472.
[48] WANG M,WANG L,HE X,et al.LncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR145/p70S6K1 and p53 pathway[J].Int J Oncol,2020,56(1):327-336.
[49] TAN Y T,LIN J F,LI T,et al.LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer[J].Cancer Commun(Lond),2021,41(2):109-120.