BACH1 is transcriptionally inhibited by TET1 in hepatocellular carcinoma in a microRNA-34a-dependent manner to regulate autophagy and inflammation.

Hepatocellular carcinoma (HCC), one of the main contributors to cancer-associated deaths globally, is characterized by high invasiveness. Herein, we studied the molecular mechanisms underlying ten-eleven translocation 1 (TET1)-mediated autophagy in HCC. Following data mining using GSE101728, GSE14520 and GSE138178, TET1 was screened out, and the differential expression of TET1 was verified by bioinformatics analysis. TET1, one of the prognostic markers in HCC, was poorly expressed in HCC. Through functional experiments, we determined that upregulation of TET1 inhibited the proliferation, migration, invasion, tumorigenesis, metastasis and inflammatory factors of HCC cells, and promoted cell autophagy and apoptosis. Mechanistically, TET1 activated miR-34a by demethylating miR-34a. BTB domain and CNC homology 1 (BACH1) was identified as the target gene of miR-34a. Notably, Downregulation of miR-34a increased cellular inflammatory factors and decreased autophagy in the presence of TET1, while declines in BACH1 suppressed cellular inflammatory factors and enhanced autophagy in the presence of miR-34a inhibitor. BACH1 negatively regulated the p53 pathway. In conclusion, TET1 is a tumor suppressor in the progression of HCC by regulating the miR-34a/BACH1/p53 axis, and may contribute to the improvement of HCC prognosis and therapy.