Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532–3p/RAB9A signal under hypoxia

• Published in: Biochemical and biophysical research communications 2021-06, Vol.557, p.26-32
• Main Authors: Ouyang, Xiwu, Yao, Lei, Liu, Guodong, Liu, Shiqing, Gong, Liansheng, Xiao, Yao
• Format: Article
• Language: English
• Subjects: Cell invasion; CircRNA; HCC; Hypoxia
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.02.120

Development of novel targeted therapies remains the priority in hepatocellular carcinoma (HCC) treatments. Early reports have demonstrated that androgen receptor (AR) plays a suppressive role in HCC progression. However, the underlying mechanisms by which AR attenuates HCC development are still elusive, especially under hypoxic conditions. Herein, we demonstrated that AR/circ-LNPEP/miR-532–3p/RAB9A signaling axis was tightly involved in hypoxia-induced cell invasion of HCC cells. AR worked as a transcription factor to reduce circ-LNPEP expression level, which released its sponge potential of miR-532–3p, leading to the downregulation of RAB9A and inhibiting cell invasion of HCC cells. In vitro and in vivo animal model also confirmed that overexpression of circ-LNPEP could reverse the suppressive effect of AR on HCC cell invasion or tumor metastasis. Overall, our study supplements a critical mechanism by which AR suppresses HCC invasion/metastasis under hypoxic conditions, providing compelling rationale to develop novel therapy for better treatments of HCC. •Circ-LNPEP acts as a novel therapeutic target for HCC.•RAB9A is the downstream of miR-532–3p that sponged by Circ-LNPEP to regulate HCC cell invasion under hypoxia.•Illustrating a new mechanism of androgen receptor regulating HCC cell invasion under hypoxia.