Background: Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC, and to explore its related mechanisms.
Methods: The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cells apoptosis was induced by nutrient-deficient culture medium, and detected by Cell Counting Kit‐8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection.
Results: HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage and lymph node metastasis. Compared with low HIF1A-AS1 group, high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines, and was increased with the prolongation of nutrient-free culture. inhibition of HIF1A-AS1 promoted starvation-induced HCC cells apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cells autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition.
Conclusions: HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cells apoptosis by reducing HIF-1α/mTOR mediated autophagy, promoting HCC cell progression.
Trial registration: This research is retrospectively registered.