Autophagy-related gene expression regulated by HIF-1α in salivary adenoid cystic carcinoma

Abstract

Objectives: Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant salivary gland tumors. Our study aims to investigate whether hypoxia-induced autophagy was up-regulated in the progression of SACC.

Materials and methods: We performed differentially expressed gene analysis and pathway enrichment analysis and then calculated the correlation analysis on GSE59701 and GSE28996 datasets. The expression of HIF-1ɑ and MAP1LC3B was analyzed in the paraffin-embedded specimens by immunohistochemical method and in the hypoxic SACC-LM cells by immunofluorescence. TEM microscopy was also performed to observe the formation of autophagosomes in SACC tissue and the hypoxic SACC-LM cells.

Results: The autophagy pathway was up-regulated in SACC datasets, and five genes including MAP1LC3B were positively correlated with HIF-1ɑ. Immunohistochemistry results showed that autophagy was activated and the expression of HIF-1ɑ and MAP1LC3B was positively correlated in SACC specimens. In hypoxic SACC-LM cells, we also identified the up-regulation of autophagy and the close correlation between HIF-1ɑ and MAP1LC3B expression. Autophagosomes were observed both in the tissue and the hypoxic SACC-LM cells by TEM microscopy.

Conclusions: Our study showed that autophagy is up-regulated in dataset, SACC tissue, and hypoxic cell line; hypoxia-induced autophagy in SACC might play a vital role in the development of SACC.

Keywords: HIF-1α; MAP1LC3B; autophagy; salivary adenoid cystic carcinoma.