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Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124.
Cell Physiol Biochem. 2018; 50(6):2188-2202.CP

Abstract

BACKGROUND/AIMS

HULC is a multifunctional lncRNA that has pro-angiogenic function in various cancers. The present study was designed to see the role of lncRNA HULC in normal endothelial cells angiogenesis.

METHODS

Cell viability, apoptosis, migration, tube formation and expression levels of angiogenesis-related proteins were respectively assessed in human microvascular endothelial HMEC-1 cells after lncRNA HULC was silenced by shRNA transfection. Cross-regulation between lncRNA HULC and miR-124, and between miR-124 and MCL-1 were detected by qRT-PCR, sequence analysis, and luciferase reporter assay.

RESULTS

Silence of lncRNA HULC significantly reduced viability, migration, tube formation and protein levels of VEGF, VEGFR2, CD144 and eNOS in HMEC-1 cells. Meanwhile, silence of lncRNA HULC induced apoptosis in HMEC-1 cells, as Bcl-2 was down-regulated, Bax was up-regulated, and caspase-3 and -9 were cleaved. miR-124 expression was negatively regulated by lncRNA HULC, and HULC worked as a molecular sponge for miR-124, in having miR-124 exhausted. Besides, MCL-1 was a target gene of miR-124. Rescue assay results showed that the effects of lncRNA HULC silence on HMEC-1 cells growth, migration and angiogenesis were abolished by miR-124 suppression. Similarly, the effects of miR-124 on HMEC-1 cells were abolished by MCL-1 overexpression. Furthermore, MCL-1 activated PI3K/AKT and JAK/STAT signaling pathways.

CONCLUSION

These findings suggest a pro-angiogenic role of lncRNA HULC in endothelial cells. The pro-angiogenic actions of lncRNA HULC may be through sponging miR-124, preventing MCL-1 from degradation by miR-124.

Authors+Show Affiliations

Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.The 4th Department of Surgery, DongFang Hospital of Beijing University of Chinese Medicine, Beijing, China.Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Chinayefeng0152@sohu.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30415256

Citation

Yin, Dexin, et al. "Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells Via Sequestrating MiR-124." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 50, no. 6, 2018, pp. 2188-2202.
Yin D, Li Y, Fu C, et al. Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124. Cell Physiol Biochem. 2018;50(6):2188-2202.
Yin, D., Li, Y., Fu, C., & Feng, Y. (2018). Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 50(6), 2188-2202. https://doi.org/10.1159/000495060
Yin D, et al. Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells Via Sequestrating MiR-124. Cell Physiol Biochem. 2018;50(6):2188-2202. PubMed PMID: 30415256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124. AU - Yin,Dexin, AU - Li,Yezhou, AU - Fu,Changgeng, AU - Feng,Ye, Y1 - 2018/11/09/ PY - 2018/01/12/received PY - 2018/11/02/accepted PY - 2018/11/12/pubmed PY - 2018/12/12/medline PY - 2018/11/12/entrez KW - Angiogenesis KW - Atherosclerosis KW - HMEC-1 cell KW - LncRNA HULC KW - MCL-1 KW - miR-124 SP - 2188 EP - 2202 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 50 IS - 6 N2 - BACKGROUND/AIMS: HULC is a multifunctional lncRNA that has pro-angiogenic function in various cancers. The present study was designed to see the role of lncRNA HULC in normal endothelial cells angiogenesis. METHODS: Cell viability, apoptosis, migration, tube formation and expression levels of angiogenesis-related proteins were respectively assessed in human microvascular endothelial HMEC-1 cells after lncRNA HULC was silenced by shRNA transfection. Cross-regulation between lncRNA HULC and miR-124, and between miR-124 and MCL-1 were detected by qRT-PCR, sequence analysis, and luciferase reporter assay. RESULTS: Silence of lncRNA HULC significantly reduced viability, migration, tube formation and protein levels of VEGF, VEGFR2, CD144 and eNOS in HMEC-1 cells. Meanwhile, silence of lncRNA HULC induced apoptosis in HMEC-1 cells, as Bcl-2 was down-regulated, Bax was up-regulated, and caspase-3 and -9 were cleaved. miR-124 expression was negatively regulated by lncRNA HULC, and HULC worked as a molecular sponge for miR-124, in having miR-124 exhausted. Besides, MCL-1 was a target gene of miR-124. Rescue assay results showed that the effects of lncRNA HULC silence on HMEC-1 cells growth, migration and angiogenesis were abolished by miR-124 suppression. Similarly, the effects of miR-124 on HMEC-1 cells were abolished by MCL-1 overexpression. Furthermore, MCL-1 activated PI3K/AKT and JAK/STAT signaling pathways. CONCLUSION: These findings suggest a pro-angiogenic role of lncRNA HULC in endothelial cells. The pro-angiogenic actions of lncRNA HULC may be through sponging miR-124, preventing MCL-1 from degradation by miR-124. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/30415256/Pro_Angiogenic_Role_of_LncRNA_HULC_in_Microvascular_Endothelial_Cells_via_Sequestrating_miR_124_ L2 - https://www.karger.com?DOI=10.1159/000495060 DB - PRIME DP - Unbound Medicine ER -