Dystrobrevin beta is a promising prognostic biomarker and therapeutic target for hepatocellular carcinoma

Objectives: Dystrobrevin beta (DTNB) is a constituent of the dystrophin-associated protein complex (DPC). Our previous RNA sequencing (RNA-seq) study revealed that knockdown of the oncogenic long noncoding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) in hepatocellular carcinoma (HCC) cells could reduce the expression levels of DTNB. However, the association between DTNB and HCC remains uncertain.

Methods: The upregulation of DTNB in HCC cell lines and the regulatory effect of HOXD-AS1 on its expression were verified using quantitative real-time PCR (qRT-PCR). The potential clinical significance, biological functions and underlying mechanisms of DTNB in HCC were investigated through bioinformatics analysis. The high expression of DTNB was validated in HCC tissues, and its biological function in HCC was investigated by performing loss-of-function assays in vitro.

Results: DTNB was highly expressed in HCC cells and was positively regulated by the lncRNA HOXD-AS1 in several HCC cell lines. The upregulation of DTNB was significantly associated with T stage, histologic grade, tumour status, adjacent hepatic tissue inflammation, alpha-fetoprotein (AFP) level, and unfavorable prognosis, serving as an independent risk indicator associated with overall survival with substantial diagnostic and prognostic implications for HCC. DTNB was also closely linked to immune cell infiltration, immunotherapy, and sensitivity to anti-HCC drugs. Genes co-expressed with DTNB in HCC were identified, and functional enrichment analysis indicated that DTNB may function in HCC by regulating the cell cycle. A potential ceRNA (competing endogenous RNA) regulatory axis of HOXD-AS1/miR-139-3p/DTNB in HCC was predicted and validated. The high expression of DTNB was validated in our HCC cohort and loss-of-function assays revealed that DTNB knockdown can suppress the proliferation, migration, and invasion of HCC cells and trigger cell cycle arrest at the G0/G1 phase.

Conclusions: DTNB, a downstream target of the lncRNA HOXD-AS1, has potential utility as a prognostic biomarker and a target for the treatment of HCC.