There is little information on the role of microRNA (miR)‑922 in the malignant behavior of liver cancer. The present study investigated the regulation of miR‑922 expression levels by cAMP response element binding protein 1 (CREB1) in liver cancer tissue, its role in regulating malignant behavior and its potential targets in liver cancer. miR‑922 expression in liver cancer cells and tissue was determined by reverse transcription‑quantitative PCR. The binding of CREB1 to the promoter region of mir‑922 was tested by chromatin immunoprecipitation‑PCR. The predicted AT‑rich interactive domain 2 (ARID2) and fidgetin, microtubule severing factor targets of miR‑922 were characterized by dual luciferase reporter assay. The effects of altered ARID2 expression levels on miR‑922‑enhanced malignant behavior of liver cancer cells were tested. CREB1 bound to the promoter region of miR‑922. Elevated miR‑922 transcripts were inversely associated with ARID2 expression in liver cancer tissue and cells. miR‑922 inhibited ARID2‑regulated luciferase expression and was present in the miR/argonaute RISC catalytic component 2 complex. ARID2 significantly decreased malignant behavior of liver cancer MHCC97L cells. Similarly, ARID2 over‑expression inhibited growth of xenograft liver cancer tumors and decreased miR‑922, Bcl‑2, proliferating cell nuclear antigen, cyclin D1, MMP3 and MMP9 expression and serum VEGF and TNF‑α levels, but enhanced Bax expression levels in tumors. ARID2 over‑expression abrogated malignant behavior promoted by miR‑922 over‑expression and enhanced miR‑922‑decreased malignant behavior of liver cancer cells. CREB induced miR‑922 transcription, which targeted ARID2 to enhance malignant behavior of liver cancer cells, indicating that the CREB1/miR‑922/ARID2 axis may be a potential target for liver cancer treatment.
Keywords: liver cancer; miRNA; CREB1; ARID2; proliferation; metastasis.