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Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma.
Oncotarget. 2016 Apr 26; 7(17):24383-401.O

Abstract

Twist1 is well known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) are involved in the EMT process and are associated with metastasis in hepatocellular carcinoma (HCC). In the present study, microRNA-26b-5p (miR-26b-5p) expression was consistently and significantly downregulated in HepG2-Twist1 HCC cell lines compared with HepG2-vector cell lines using microarrays (the HepG2-Twist1 cell line can stably express Twist1). miR-26b- 5p downregulation was directly mediated by Twist1 through binding to the promoter region of miR-26b-5p in HepG2-Twist1 cells by ChIP-seq technology. Both gain- and loss-of-function studies showed that miR-26b-5p dramatically suppressed EMT and the invasion ability of HCC cells in vitro. Using mouse models, tumors derived from miR- 26b-5p-overexpressed HCC cells exhibited a significant reduction in tumorigenicity compared with the control group. Subsequent investigation revealed that miR-26b-5p directly inhibited SMAD family member 1 (SMAD1) expression. miR-26b-5p repressed BMP4/Smad1 signaling following SMAD1 inhibition. Overexpression of SMAD1 reversed the function of miR-26b-5p. In human HCC tissues and mouse xenograft tumors, miR-26b-5p levels were inversely correlated with SMAD1 expression as well as metastasis.

CONCLUSION

miR-26b-5p suppresses Twist1-induced EMT, invasion, and metastasis of HCC cells by targeting SMAD1 and BMP4/Smad1 signaling. This suggests a promising application for miR-26b-5p in anti-HCC therapy.

Authors+Show Affiliations

Department of Pathology, Tianjin Medical University, Tianjin 300070, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China. Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China.Department of Prosthodontics, Affiliated Stomatological Hospital, Tianjin Medical University, Tianjin 300070, China.Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China.Department of Pathology, Tianjin Medical University, Tianjin 300070, China.Department of Pathology, Mudanjiang Medical University, Heilongjiang 157011, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27027434

Citation

Wang, Yong, et al. "Twist1-related miR-26b-5p Suppresses Epithelial-mesenchymal Transition, Migration and Invasion By Targeting SMAD1 in Hepatocellular Carcinoma." Oncotarget, vol. 7, no. 17, 2016, pp. 24383-401.
Wang Y, Sun B, Zhao X, et al. Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma. Oncotarget. 2016;7(17):24383-401.
Wang, Y., Sun, B., Zhao, X., Zhao, N., Sun, R., Zhu, D., Zhang, Y., Li, Y., Gu, Q., Dong, X., Wang, M., & An, J. (2016). Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma. Oncotarget, 7(17), 24383-401. https://doi.org/10.18632/oncotarget.8328
Wang Y, et al. Twist1-related miR-26b-5p Suppresses Epithelial-mesenchymal Transition, Migration and Invasion By Targeting SMAD1 in Hepatocellular Carcinoma. Oncotarget. 2016 Apr 26;7(17):24383-401. PubMed PMID: 27027434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma. AU - Wang,Yong, AU - Sun,Baocun, AU - Zhao,Xiulan, AU - Zhao,Nan, AU - Sun,Ran, AU - Zhu,Dongwang, AU - Zhang,Yanhui, AU - Li,Yanlei, AU - Gu,Qiang, AU - Dong,Xueyi, AU - Wang,Meili, AU - An,Jindan, PY - 2015/09/30/received PY - 2016/03/04/accepted PY - 2016/3/31/entrez PY - 2016/3/31/pubmed PY - 2017/12/5/medline KW - SMAD1 KW - early recurrence KW - epithelial-mesenchymal transition KW - hepatocellular carcinoma KW - microRNA SP - 24383 EP - 401 JF - Oncotarget JO - Oncotarget VL - 7 IS - 17 N2 - UNLABELLED: Twist1 is well known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) are involved in the EMT process and are associated with metastasis in hepatocellular carcinoma (HCC). In the present study, microRNA-26b-5p (miR-26b-5p) expression was consistently and significantly downregulated in HepG2-Twist1 HCC cell lines compared with HepG2-vector cell lines using microarrays (the HepG2-Twist1 cell line can stably express Twist1). miR-26b- 5p downregulation was directly mediated by Twist1 through binding to the promoter region of miR-26b-5p in HepG2-Twist1 cells by ChIP-seq technology. Both gain- and loss-of-function studies showed that miR-26b-5p dramatically suppressed EMT and the invasion ability of HCC cells in vitro. Using mouse models, tumors derived from miR- 26b-5p-overexpressed HCC cells exhibited a significant reduction in tumorigenicity compared with the control group. Subsequent investigation revealed that miR-26b-5p directly inhibited SMAD family member 1 (SMAD1) expression. miR-26b-5p repressed BMP4/Smad1 signaling following SMAD1 inhibition. Overexpression of SMAD1 reversed the function of miR-26b-5p. In human HCC tissues and mouse xenograft tumors, miR-26b-5p levels were inversely correlated with SMAD1 expression as well as metastasis. CONCLUSION: miR-26b-5p suppresses Twist1-induced EMT, invasion, and metastasis of HCC cells by targeting SMAD1 and BMP4/Smad1 signaling. This suggests a promising application for miR-26b-5p in anti-HCC therapy. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27027434/Twist1_related_miR_26b_5p_suppresses_epithelial_mesenchymal_transition_migration_and_invasion_by_targeting_SMAD1_in_hepatocellular_carcinoma_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=8328 DB - PRIME DP - Unbound Medicine ER -