HAX1 maintains the glioma progression in hypoxia through promoting mitochondrial fission

Abstract

HCLS1-associated protein X-1 (HAX1), an anti-apoptotic molecular, overexpresses in glioma. However, the role of HAX1 in glioma cell surviving in hypoxic environment remains unclear. Western blotting, qRT-PCR, Transwell assay, TUNEL assay, wounding healing assay, clone formation, tumour xenograft model and immunohistochemical staining were used to investigate the role of HAX1 in glioma. HAX1 regulated by HIF-1α was increased in glioma cells cultured in hypoxia. Silencing of HAX1 could cause an increased apoptosis of glioma cells cultured in hypoxia. Silencing of HAX1 also decreased the proliferation, migration and invasion of glioma cells cultured in hypoxia. Increased mitochondrial fission could prevent glioma cells from the damage induced by HAX1 knockdown in hypoxia. Furthermore, HAX1 was found to regulate glioma cells through phosphorylated AKT/Drp signal pathway. In conclusion, our study suggested that HAX1 promoted survival of glioma cells in hypoxic environment via AKT/Drp signal pathway. Our study also provided a potential therapeutic target for glioma.

NOD1 cooperates with HAX‐1 to promote cell migration in a RIPK2‐ and NF‐ĸB‐independent manner

“…In line with the literature, silencing of HAX-1 attenuated cell migration in our HeLa cell model [25][26][27][28]. Additional knockdown of NOD1 did not further decrease cell migration.…”

“…This was shown for colorectal cancer [20], oesophageal squamous cell carcinoma [21,22], lung cancer [23], melanoma [23], breast cancer [23], liver cancer [24,25] and ovarian cancer [26]. HAX‐1 knockdown reduced cell migration in hepatocellular [25], ovarian [26] and glioma [27] cancer cells. More specifically, in one study silencing of HAX‐1 did not attenuate single‐cell migration, but collective cell migration, which was due to reduced cell–cell and cell–extracellular matrix (ECM) contacts [28].…”