LncRNA MALAT1 functions as a competing endogenous RNA to regulate ZEB2 expression by sponging miR-200s in clear cell kidney carcinoma

Long non-coding RNA (lncRNAs) play a critical role in the development of cancers. LncRNA metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, bladder cancer and so on. Here, we found that MALAT1 exist a higher fold change (Tumor/Normal) in clear cell kidney carcinoma (KIRC) from The Cancer Genome Atlas (TCGA) Data Portal and a negative correlation with miR-200s family. We further demonstrated MALAT1 promote KIRC proliferation and metastasis through sponging miR-200s in vitro and in vivo. In addition, miR-200c can partly reverse the MALAT1′s stimulation on proliferation and metastasis in KIRC. In summary we unveil a branch of the MALAT1/miR-200s/ZEB2 pathway that regulates the progression of KIRC. The inhibition of MALAT1 expression may be a promising strategy for KIRC therapy.

[1]  Pieter C. Dorrestein,et al.  ncRNA- and Pc2 Methylation-Dependent Gene Relocation between Nuclear Structures Mediates Gene Activation Programs , 2011, Cell.

[2]  Hui Zhou,et al.  starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data , 2013, Nucleic Acids Res..

[3]  P. Pandolfi,et al.  A coding-independent function of gene and pseudogene mRNAs regulates tumour biology , 2010, Nature.

[4]  Michael Y Tolstorukov,et al.  The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. , 2014, Molecular cell.

[5]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[6]  Yongjun Tan,et al.  FOXA2 attenuates the epithelial to mesenchymal transition by regulating the transcription of E-cadherin and ZEB2 in human breast cancer. , 2015, Cancer letters.

[7]  M. Gorospe,et al.  Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB , 2013, PLoS genetics.

[8]  Rajvir Dahiya,et al.  Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205. , 2015, Cancer research.

[9]  G. Goodall,et al.  The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 , 2008, Nature Cell Biology.

[10]  B. Blencowe,et al.  The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. , 2010, Molecular cell.

[11]  J. Steitz,et al.  Formation of triple-helical structures by the 3′-end sequences of MALAT1 and MENβ noncoding RNAs , 2012, Proceedings of the National Academy of Sciences.

[12]  Z. Cai,et al.  Hsa‐miR‐125b suppresses bladder cancer development by down‐regulating oncogene SIRT7 and oncogenic long non‐coding RNA MALAT1 , 2013, FEBS letters.

[13]  K. Dahlman-Wright,et al.  AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into TNFα-induced epithelial–mesenchymal transition in triple-negative breast cancer , 2015, Oncotarget.

[14]  D. Cacchiarelli,et al.  A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA , 2011, Cell.

[15]  N. Seki,et al.  Epithelial–mesenchymal transition-related microRNA-200s regulate molecular targets and pathways in renal cell carcinoma , 2013, Journal of Human Genetics.

[16]  Michael Thomas,et al.  MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer , 2003, Oncogene.

[17]  S. Diederichs,et al.  MALAT1 — a paradigm for long noncoding RNA function in cancer , 2013, Journal of Molecular Medicine.

[18]  J. Eberwine,et al.  Immunoprecipitation of mRNA-protein complexes , 2006, Nature Protocols.

[19]  Anders H. Lund,et al.  microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus , 2013, Scientific Reports.

[20]  K. Tang,et al.  Prognostic value of meta-signature miRNAs in renal cell carcinoma: an integrated miRNA expression profiling analysis , 2015, Scientific Reports.

[21]  Xing-Sui Lu,et al.  miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression , 2014, Clinical Cancer Research.

[22]  Qihong Huang,et al.  Pseudogene PTENP1 Functions as a Competing Endogenous RNA to Suppress Clear-Cell Renal Cell Carcinoma Progression , 2014, Molecular Cancer Therapeutics.

[23]  Meng Li,et al.  Silencing of Long Noncoding RNA MALAT1 by miR-101 and miR-217 Inhibits Proliferation, Migration, and Invasion of Esophageal Squamous Cell Carcinoma Cells* , 2014, The Journal of Biological Chemistry.

[24]  D. Spector,et al.  The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. , 2013, Cancer research.

[25]  W Marston Linehan,et al.  Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics , 2012, Genome research.

[26]  Ping Wang,et al.  Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326 , 2015, Oncotarget.

[27]  F. Liu,et al.  A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. , 2014, Cancer cell.

[28]  Fuqing Zeng,et al.  Overexpression of SATB1 Is Associated with Biologic Behavior in Human Renal Cell Carcinoma , 2014, PloS one.

[29]  Y. Nie,et al.  Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression , 2014, Hepatology.

[30]  H. Al-Ahmadie,et al.  Recent developments in the pathology of renal tumors: morphology and molecular characteristics of select entities. , 2009, Archives of pathology & laboratory medicine.

[31]  Junhua Zheng,et al.  Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma , 2015, Tumor Biology.

[32]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[33]  Lorenzo Farina,et al.  Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer , 2014, BMC Systems Biology.

[34]  Phillip A Sharp,et al.  A triple helix stabilizes the 3' ends of long noncoding RNAs that lack poly(A) tails. , 2012, Genes & development.

[35]  Zhiquan Hu,et al.  Epigenetic alterations of Krüppel-like factor 4 and its tumor suppressor function in renal cell carcinoma. , 2013, Carcinogenesis.

[36]  Jun‐hang Luo,et al.  Protein Expression of ZEB2 in Renal Cell Carcinoma and Its Prognostic Significance in Patient Survival , 2013, PloS one.