Long non‑coding RNA metastasis‑associated lung adenocarcinoma transcript 1 regulates renal cancer cell migration via cofilin‑1 Corrigendum in /10.3892/ol.2021.12622

Zhang,Yali; Guan,Xinyu; Wang,Hao; Wang,Yong; Yue,Dan; Chen,Ruibing

doi:10.3892/ol.2020.11914

Long non‑coding RNA metastasis‑associated lung adenocarcinoma transcript 1 regulates renal cancer cell migration via cofilin‑1

Corrigendum in: /10.3892/ol.2021.12622

Authors:
- Yali Zhang
- Xinyu Guan
- Hao Wang
- Yong Wang
- Dan Yue
- Ruibing Chen
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Affiliations: Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300070, P.R. China, School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. China, School of Pharmaceutical Science and Technology, Health Science Platform, Tianjin University, Tianjin 300072, P.R. China
Published online on: July 27, 2020 https://doi.org/10.3892/ol.2020.11914
Article Number: 53
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA (lncRNA) metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in numerous types of cancer, and is implicated in various cellular processes associated with cancer progression. However, the underlying molecular mechanisms by which MALAT1 regulates metastasis remain unclear. The present study investigated the expression of MALAT1 across a range of different cancer types by analyzing RNA sequencing data from The Cancer Genome Atlas database. The results indicate that the expression of MALAT1 is highly tissue‑dependent and that MALAT1 is significantly overexpressed in renal clear cell carcinoma (KIRC). The biological role of MALAT1 in regulating KIRC cell migration was further investigated using molecular and cellular assays. The results demonstrate that MALAT1 regulates the expression of cofilin‑1 (CFL1), potentially by regulating RNA splicing. MALAT1 knockdown decreased the expression of CFL1 at both the mRNA and protein levels, and affected cytoskeletal rearrangement by regulating the levels of F‑actin via CFL1, leading to significantly decreased cellular migration. Clinical analysis confirmed a significant correlation between MALAT1 and CFL1 expression, implicating both genes as biomarkers for poor prognosis in KIRC. The present study demonstrates a novel mechanism by which MALAT1 regulates cell migration, which may be exploited to develop novel therapeutic strategies for managing renal cancer metastasis.

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1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Source, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
3	Lopez-Beltran A, Carrasco JC, Cheng L, Scarpelli M, Kirkali Z and Montironi R: 2009 update on the classification of renal epithelial tumours in adults. Int J Urol. 16:432–443. 2009. View Article : Google Scholar : PubMed/NCBI
4	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI
5	Bedke J, Gauler T, Grünwald V, Hegele A, Herrmann E, Hinz S, Janssen J, Schmitz S, Schostak M, Tesch H, et al: Systemic therapy in metastatic renal cell carcinoma. World J Urol. 35:179–188. 2017. View Article : Google Scholar : PubMed/NCBI
6	Brown C: Targeted therapy: An elusive cancer target. Nature. 537:S106–S108. 2016. View Article : Google Scholar : PubMed/NCBI
7	Ulitsky I and Bartel DP: LincRNAs: Genomics, evolution, and mechanisms. Cell. 154:26–46. 2013. View Article : Google Scholar : PubMed/NCBI
8	Yang L, Lin C, Jin C, Yang JC, Tanasa B, Li W, Merkurjev D, Ohgi KA, Meng D, Zhang J, et al: LncRNA-dependent mechanisms of androgen receptor-regulated gene activation programs. Nature. 500:598–602. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wilusz JE: Long noncoding RNAs: Re-writing dogmas of RNA processing and stability. Biochim Biophys Acta. 1859:128–138. 2016. View Article : Google Scholar : PubMed/NCBI
10	Gutschner T, Hämmerle M and Diederichs S: MALAT1-a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl). 91:791–801. 2013. View Article : Google Scholar : PubMed/NCBI
11	Gutschner T, Hämmerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, et al: The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 73:1180–1189. 2013. View Article : Google Scholar : PubMed/NCBI
12	Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, et al: MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 22:8031–8041. 2003. View Article : Google Scholar : PubMed/NCBI
13	Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI
14	Hu L, Wu Y, Tan D, Meng H, Wang K, Bai Y and Yang K: Up-regulation of long noncoding RNA MALAT1 contributes to proliferation and metastasis in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 34:72015. View Article : Google Scholar : PubMed/NCBI
15	Okugawa Y, Toiyama Y, Hur K, Toden S, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Kusunoki M, Boland CR and Goel A: Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. Carcinogenesis. 35:2731–2739. 2014. View Article : Google Scholar : PubMed/NCBI
16	Park JY, Lee JE, Park JB, Yoo H, Lee SH and Kim JH: Roles of long non-coding RNAs on tumourigenesis and glioma development. Brain Tumour Res Treat. 2:1–6. 2014. View Article : Google Scholar
17	Xiao H, Tang K, Liu P, Chen K, Hu J, Zeng J, Xiao W, Yu G, Yao W, Zhou H, et al: LncRNA MALAT1 functions as a competing endogenous RNA to regulate ZEB2 expression by sponging miR-200s in clear cell kidney carcinoma. Oncotarget. 6:38005–38015. 2015. View Article : Google Scholar : PubMed/NCBI
18	Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, et al: The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 39:925–938. 2010. View Article : Google Scholar : PubMed/NCBI
19	Chen R, Liu Y, Zhuang H, Yang B, Hei K, Xiao M, Hou C, Gao H, Zhang X, Jia C, et al: Quantitative proteomics reveals that long non-coding RNA MALAT1 interacts with DBC1 to regulate p53 acetylation. Nucleic Acids Res. 45:9947–9959. 2017. View Article : Google Scholar : PubMed/NCBI
20	Engreitz JM, Sirokman K, McDonel P, Shishkin AA, Surka C, Russell P, Grossman SR, Chow AY, Guttman M and Lander ES: RNA-RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell. 159:188–199. 2014. View Article : Google Scholar : PubMed/NCBI
21	Dawe HR, Minamide LS, Bamburg JR and Cramer LP: ADF/cofilin controls cell polarity during fibroblast migration. Curr Biol. 13:252–257. 2003. View Article : Google Scholar : PubMed/NCBI
22	Wang W, Eddy R and Condeelis J: The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer. 7:429–440. 2007. View Article : Google Scholar : PubMed/NCBI
23	Bravo-Cordero JJ, Magalhaes MA, Eddy RJ, Hodgson L and Condeelis J: Functions of cofilin in cell locomotion and invasion. Nat Rev Mol Cell Biol. 14:405–415. 2013. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Warren AY and Harrison D: WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: Standards and controversies. World J Urol. 36:1913–1926. 2018. View Article : Google Scholar : PubMed/NCBI
26	Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, et al: TCGAbiolinks: An R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 44:e712016. View Article : Google Scholar : PubMed/NCBI
27	R Core Team (2012), . R: A language and environment for statistical computing. R Foundation for Statistical Computing. (Vienna, Austria). ISBN 3-900051-07-0, URL http://www.R-project.org/.
28	RStudio Team (2015), . RStudio: Integrated Development for R. RStudio, Inc. (Boston, MA). URL http://www.rstudio.com/.
29	Rooney MS, Shukla SA, Wu CJ, Getz G and Hacohen N: Molecular and genetic properties of tumours associated with local immune cytolytic activity. Cell. 160:48–61. 2015. View Article : Google Scholar : PubMed/NCBI
30	Yu G, Wang LG, Han Y and He QY: ClusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 16:284–287. 2012. View Article : Google Scholar : PubMed/NCBI
31	Zhang HM, Yang FQ, Chen SJ, Che J and Zheng JH: Upregulation of long non-coding RNA MALAT1 correlates with tumour progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol. 36:2947–2955. 2015. View Article : Google Scholar : PubMed/NCBI
32	Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, Ishii N and Dahiya R: Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res. 75:1322–1331. 2015. View Article : Google Scholar : PubMed/NCBI
33	Han Y, Liu Y, Zhang H, Wang T, Diao R, Jiang Z, Gui Y and Cai Z: Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long non-coding RNA MALAT1. FEBS Lett. 587:3875–3882. 2013. View Article : Google Scholar : PubMed/NCBI
34	Malakar P, Shilo A, Mogilevsky A, Stein I, Pikarsky E, Nevo Y, Benyamini H, Elgavish S, Zong X, Prasanth KV and Karni R: Long noncoding RNA MALAT1 promotes hepatocellular carcinoma development by SRSF1 upregulation and mTOR activation. Cancer Res. 77:1155–1167. 2017. View Article : Google Scholar : PubMed/NCBI
35	Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, Zhang Y, Gorospe M, Prasanth SG, Lal A and Prasanth KV: Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 9:e10033682013. View Article : Google Scholar : PubMed/NCBI
36	Kim J, Piao HL, Kim BJ, Yao F, Han Z, Wang Y, Xiao Z, Siverly AN, Lawhon SE, Ton BN, et al: Long noncoding RNA MALAT1 suppresses breast cancer metastasis. Nat Genet. 50:1705–1715. 2018. View Article : Google Scholar : PubMed/NCBI
37	Li C, Miao R, Liu S, Wan Y, Zhang S, Deng Y, Bi J, Qu K, Zhang J and Liu C: Down-regulation of miR-146b-5p by long noncoding RNA MALAT1 in hepatocellular carcinoma promotes cancer growth and metastasis. Oncotarget. 8:28683–28695. 2017. View Article : Google Scholar : PubMed/NCBI
38	Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, Dorrestein PC and Rosenfeld MG: ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell. 147:773–788. 2011. View Article : Google Scholar : PubMed/NCBI
39	Sun Z, Ou C, Liu J, Chen C, Zhou Q, Yang S, Li G, Wang G, Song J, Li Z, et al: YAP1-induced MALAT1 promotes epithelial-mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer. Oncogene. 38:2627–2644. 2019. View Article : Google Scholar : PubMed/NCBI
40	Audibert A, Weil D and Dautry F: In vivo kinetics of mRNA splicing and transport in mammalian cells. Mol Cell Biol. 22:6706–6718. 2002. View Article : Google Scholar : PubMed/NCBI
41	Chen Q and Pollard TD: Actin filament severing by cofilin is more important for assembly than constriction of the cytokinetic contractile ring. J Cell Biol. 195:485–498. 2011. View Article : Google Scholar : PubMed/NCBI
42	Kanellos G, Zhou J, Patel H, Ridgway RA, Huels D, Gurniak CB, Sandilands E, Carragher NO, Sansom OJ, Witke W, et al: ADF and cofilin1 control actin stress fibres, nuclear integrity, and cell survival. Cell Rep. 13:1949–1964. 2015. View Article : Google Scholar : PubMed/NCBI
43	Pang D, Yang C, Li C, Zou Y, Feng B, Li L, Liu W, Luo Q, Chen Z and Huang C: Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway. Biol Open. 9:bio0468542020. View Article : Google Scholar : PubMed/NCBI