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Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139.
Cell Physiol Biochem. 2017; 44(3):857-869.CP

Abstract

BACKGROUND/AIMS

Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells.

METHODS

Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis.

RESULTS

Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells.

CONCLUSION

These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.

Authors+Show Affiliations

Department of Cardiovascular Internal Medicine, Changchun, China.Department of Cardiovascular Internal Medicine, Changchun, China.Department of Cardiovascular Internal Medicine, Changchun, China.Department of Gastrointestinal Surgery, Changchun, China.Department of Clinical Laboratory, China-Japan Union Hospital of Jilin University, Changchun, China.Department of Cardiovascular Internal Medicine, Changchun, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29179202

Citation

Gong, Li-Cheng, et al. "Long Non-Coding RNA H19 Protects H9c2 Cells Against Hypoxia-Induced Injury By Targeting MicroRNA-139." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 44, no. 3, 2017, pp. 857-869.
Gong LC, Xu HM, Guo GL, et al. Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139. Cell Physiol Biochem. 2017;44(3):857-869.
Gong, L. C., Xu, H. M., Guo, G. L., Zhang, T., Shi, J. W., & Chang, C. (2017). Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 44(3), 857-869. https://doi.org/10.1159/000485354
Gong LC, et al. Long Non-Coding RNA H19 Protects H9c2 Cells Against Hypoxia-Induced Injury By Targeting MicroRNA-139. Cell Physiol Biochem. 2017;44(3):857-869. PubMed PMID: 29179202.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139. AU - Gong,Li-Cheng, AU - Xu,Hai-Ming, AU - Guo,Gong-Liang, AU - Zhang,Tao, AU - Shi,Jing-Wei, AU - Chang,Chang, Y1 - 2017/11/24/ PY - 2017/04/12/received PY - 2017/10/14/accepted PY - 2017/11/28/pubmed PY - 2018/1/19/medline PY - 2017/11/28/entrez KW - Acute myocardial infarction KW - Long non-coding RNA H19 KW - MAPK KW - MTOR KW - MiR-139 KW - PI3K/AKT KW - Sox8 SP - 857 EP - 869 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 44 IS - 3 N2 - BACKGROUND/AIMS: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. METHODS: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. RESULTS: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. CONCLUSION: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/29179202/Long_Non_Coding_RNA_H19_Protects_H9c2_Cells_against_Hypoxia_Induced_Injury_by_Targeting_MicroRNA_139_ L2 - https://www.karger.com?DOI=10.1159/000485354 DB - PRIME DP - Unbound Medicine ER -