Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis

  • Hua Liu The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, China https://orcid.org/0000-0002-0035-9086
  • Yan Yin Respiratory and Critical Care Medicine of Tianjin Chest Hospital, Tianjin, China
  • Ting Liu Tianjin Institute of Cardiovascular Disease, Tianjin Chest Hospital, Tianjin, China https://orcid.org/0000-0002-4173-8963
  • Yanying Gao The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, China https://orcid.org/0000-0002-8893-9295
  • Qing Ye The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, China https://orcid.org/0000-0001-5205-237X
  • Junqing Yan The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, China https://orcid.org/0000-0002-8715-5341
  • Fushuang Ha The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, China https://orcid.org/0000-0001-6951-2432
Keywords: PVT1, miR-3619-5p, MKL1, cell migration, hepatocellular carcinoma, HCC

Abstract

Hepatocellular carcinoma (HCC) is the third most common malignant tumor of the digestive system. Plasma cell tumor heterotopic gene 1 (PVT1) is an intergenic long non-coding RNA that is aberrantly expressed in different cancers. Myocardin-related transcription factor A or megakaryoblastic leukemia 1 (MKL1) is a transcriptional coactivator of serum response factor that has been shown to promote cancer cell migration and invasion. In this study, we investigated the relationship between PVT1 and MKL1 as a novel regulatory mechanism underlying HCC progression. We used HepG2 and Cos‑7 cell lines. Transfection experiments with miR-3619-5p mimics/inhibitor, PVT1, siRNA-PVT1, MKL1, or siRNA-MKL1 were performed. RNA and protein levels were analyzed by quantitative reverse transcription PCR and Western blot, respectively. Cell migration was assessed by transwell assay. Luciferase assays, RNA-FISH, RNA immunoprecipitation, and chromatin immunoprecipitation assays were performed to confirm the interaction between PVT1, miR-3619-5p, and MKL1 in HCC cells. Overexpression of PVT1 was positively correlated with MKL1 upregulation, which promoted HepG2 cell migration. miR-3619-5p inhibited MKL1 expression in HCC cells by acting on its 3′-UTR. Furthermore, PVT1 promoted MKL1 expression and migration in HCC cells by directly binding to miR-3619-5p. In a positive feedback loop, MKL1 could activate PVT1 transcription by binding to the CArG box in the promoter region. Our findings may provide a basis for the development of novel targeted therapies in HCC.

Downloads

Download data is not yet available.
Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis
Published
2020-02-26
How to Cite
1.
Liu H, Yin Y, Liu T, Gao Y, Ye Q, Yan J, Ha F. Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis. Bosn J of Basic Med Sci [Internet]. 2020Feb.26 [cited 2020Jul.7];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/4641
Section
Molecular Biology