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lncRNA H19 regulates epithelial-mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA.
Biochim Biophys Acta Mol Cell Res 2017; 1864(10):1887-1899BB

Abstract

Accumulating evidences indicate that long noncoding RNAs (lncRNAs) might play important roles in tumorigenesis and metastasis. EMT (epithelial-to-mesenchymal transition) is considered as a critical step in invasion and metastasis of various tumors including bladder cancer (BC). Recent researches have showed that lncRNA H19 is implicated in metastasis through regulating EMT and the reverse MET (mesenchymal-to-epithelial transition). However, underlying mechanisms remain largely unknown. Here, we screened lncRNA and mRNA expression profiles of BC with microarray assay. We found that H19 and DNMT3B displayed a higher co-expression in BC tissues and cells. Functionally, we demonstrated that H19 could increase proliferation, invasion and migration, regulate EMT as well as rearrange cytoskeleton of BC cells in vitro. Moreover, ectopic expression of H19 promoted tumorigenesis, angiogenesis and pulmonary metastasis in vivo, whereas knockdown of H19 has a contrary role in vivo and in vitro. Mechanistically, we proved that H19 could directly bind to miR-29b-3p (miR-29b) and derepress the expression of target DNMT3B. H19 and miR-29b-3p showed a co-localization. More importantly, up-regulating H19 antagonized miR-29b-3p-mediated proliferation, migration and EMT suppression in BC cells. Furthermore, H19 knockdown partially reversed the function of miR-29b-3p inhibitor on DNMT3B and facilitated miR-29b-3p-induced MET. Taken together, we demonstrated for the first time that H19 might function as ceRNA (competing endogenous RNA) for miR-29b-3p and relieve the suppression for DNMT3B, which led to EMT and metastasis of BC. Our findings highlight a novel mechanism of H19 in progression of BC and provide H19/miR-29b-3p/DNMT3B axis as a promising therapeutic target for BC.

Authors+Show Affiliations

Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, PR China.The First Clinical College, Chongqing Medical University, Chongqing 400016, PR China.College of Clinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan, PR China.Department of Cell Biology and Genetics, Southwest Medical University, Luzhou 646000, Sichuan, PR China.Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing, PR China.Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: chjunxia@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28779971

Citation

Lv, Mengxin, et al. "LncRNA H19 Regulates Epithelial-mesenchymal Transition and Metastasis of Bladder Cancer By miR-29b-3p as Competing Endogenous RNA." Biochimica Et Biophysica Acta. Molecular Cell Research, vol. 1864, no. 10, 2017, pp. 1887-1899.
Lv M, Zhong Z, Huang M, et al. LncRNA H19 regulates epithelial-mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA. Biochim Biophys Acta Mol Cell Res. 2017;1864(10):1887-1899.
Lv, M., Zhong, Z., Huang, M., Tian, Q., Jiang, R., & Chen, J. (2017). LncRNA H19 regulates epithelial-mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA. Biochimica Et Biophysica Acta. Molecular Cell Research, 1864(10), pp. 1887-1899. doi:10.1016/j.bbamcr.2017.08.001.
Lv M, et al. LncRNA H19 Regulates Epithelial-mesenchymal Transition and Metastasis of Bladder Cancer By miR-29b-3p as Competing Endogenous RNA. Biochim Biophys Acta Mol Cell Res. 2017;1864(10):1887-1899. PubMed PMID: 28779971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - lncRNA H19 regulates epithelial-mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA. AU - Lv,Mengxin, AU - Zhong,Zhenyu, AU - Huang,Mengge, AU - Tian,Qiang, AU - Jiang,Rong, AU - Chen,Junxia, Y1 - 2017/08/02/ PY - 2017/03/14/received PY - 2017/07/27/revised PY - 2017/08/01/accepted PY - 2017/8/7/pubmed PY - 2017/12/7/medline PY - 2017/8/7/entrez KW - Bladder cancer KW - EMT KW - Metastasis KW - ceRNA KW - lncRNA H19 KW - miR-29 SP - 1887 EP - 1899 JF - Biochimica et biophysica acta. Molecular cell research JO - Biochim Biophys Acta Mol Cell Res VL - 1864 IS - 10 N2 - Accumulating evidences indicate that long noncoding RNAs (lncRNAs) might play important roles in tumorigenesis and metastasis. EMT (epithelial-to-mesenchymal transition) is considered as a critical step in invasion and metastasis of various tumors including bladder cancer (BC). Recent researches have showed that lncRNA H19 is implicated in metastasis through regulating EMT and the reverse MET (mesenchymal-to-epithelial transition). However, underlying mechanisms remain largely unknown. Here, we screened lncRNA and mRNA expression profiles of BC with microarray assay. We found that H19 and DNMT3B displayed a higher co-expression in BC tissues and cells. Functionally, we demonstrated that H19 could increase proliferation, invasion and migration, regulate EMT as well as rearrange cytoskeleton of BC cells in vitro. Moreover, ectopic expression of H19 promoted tumorigenesis, angiogenesis and pulmonary metastasis in vivo, whereas knockdown of H19 has a contrary role in vivo and in vitro. Mechanistically, we proved that H19 could directly bind to miR-29b-3p (miR-29b) and derepress the expression of target DNMT3B. H19 and miR-29b-3p showed a co-localization. More importantly, up-regulating H19 antagonized miR-29b-3p-mediated proliferation, migration and EMT suppression in BC cells. Furthermore, H19 knockdown partially reversed the function of miR-29b-3p inhibitor on DNMT3B and facilitated miR-29b-3p-induced MET. Taken together, we demonstrated for the first time that H19 might function as ceRNA (competing endogenous RNA) for miR-29b-3p and relieve the suppression for DNMT3B, which led to EMT and metastasis of BC. Our findings highlight a novel mechanism of H19 in progression of BC and provide H19/miR-29b-3p/DNMT3B axis as a promising therapeutic target for BC. SN - 0167-4889 UR - https://www.unboundmedicine.com/medline/citation/28779971/lncRNA_H19_regulates_epithelial_mesenchymal_transition_and_metastasis_of_bladder_cancer_by_miR_29b_3p_as_competing_endogenous_RNA_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-4889(17)30206-9 DB - PRIME DP - Unbound Medicine ER -