lncDILC Downregulation in Liver Cancer-Associated Fibroblasts Drives Pro-Invasive Conversion via a miR-6071-ZNF395 Axis.

Cancer-associated fibroblasts (CAFs) play important roles in the progression of hepatocarcinoma, while the mechanism underlying the pro-invasive transformation of normal fibroblasts (NFs) to CAFs remains poorly defined. lncDILC is a long non-coding RNA previously identified to be downregulated in liver cancer stem cells. Here, we found that lncDILC was also significantly downregulated in liver cancer CAFs compared with NFs. Knockdown of lncDILC in NFs facilitated their conversion into CAFs, and enhanced the ability to promote the migration and invasion of liver cancer cells. Conversely, overexpression of lncDILC in CAFs ameliorated their invasive characteristics, and suppressed cancer cell metastasis. Moreover, we found miR-6071 acted as a target of lncDILC, and functioned as a transcriptive suppressor of zinc finger protein 395 (ZNF395), which exhibited an inhibitory effect on the pro-invasive conversion of fibroblasts. Overexpression of ZNF395 reversed the pro-invasive effects induced by lncDILC knockdown. These results elucidate a pathway of lncDILC-miR-6071-ZNF395 that suppresses the NF-CAF conversion, suggesting new therapeutic targets for the strategies for the treatment of liver cancer.