Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis

Yongbo Zhao, Guangxing Feng, Yanzhi Wang, Yuehong Yue, Weichao Zhao
International Journal of Clinical and Experimental Pathology 2014, 7 (11): 7643-52

OBJECTIVE: Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as transcriptional regulation, cell growth and tumorigenesis. However, little was known about whether lncRNA HIF 1 alpha-antisense RNA 1 (HIF1a-AS1) in regulating the proliferation and apoptosis of VSMCs in vitro and the expression of HIF1a-AS1 in serum of TAA patients.

METHODS: The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. Cells were transfected with siRNAs as a gene silencing methods.

RESULTS: In serum of TAA patients, the expression of HIF1a-AS1 was significantly increased (superior to 6 folds) compared to the normal control. Moreover, PA induced cell apoptosis in VSMCs in a time- and dose-dependent manner, and the proportion of the apoptotic cells had gained as compared to untreatment group. PA also induced upregulation expression of HIF1a-AS1. We also found that transfection of cells with HIF1a-AS1 siRNA decreased the expression of caspase3 and caspase8 and increased the expression of Bcl2, and protected PA-induced cell apoptosis in VSMCs.

CONCLUSIONS: HIF1a-AS1 was overexpressed in the thoracoabdominal aorta aneurysm and the interaction between HIF1a-AS1 and apoptotic proteins plays a key role in the proliferation and apoptosis of VSMCs in vitro, which may contribute to the pathogenesis of thoracoabdominal aorta aneurysm.

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