Effects of FER1L4-miR-106a-5p/miR-372-5p-E2F1 regulatory axis on drug resistance in liver cancer chemotherapy

• Main Authors: Xu Wang (Author), Yunfei Chen (Author), Ke Dong (Author), Yujing Ma (Author), Qizhi Jin (Author), Shujun Yin (Author), Xiaoshi Zhu (Author), Shan Wang (Author)
• Format: Book
• Published: Elsevier, 2021-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2162-2531; 10.1016/j.omtn.2021.02.006
• Keywords: FER1L4; miR-106a-5p; miR-372-5p; E2F1; NF-κB; liver cancer; Therapeutics. Pharmacology; RM1-950
• Source: Molecular Therapy: Nucleic Acids, Vol 24, Iss , Pp 449-461 (2021)

Liver cancer presents a challenge in today's healthcare system. This study aimed at investigating the effects of Fer-1 like family member 4 (FER1L4) on chemotherapy resistance and liver cancer development by using clinically collected liver cancer tissues and commercially purchased human liver cancer cisplatin-resistant cell line HUH-7/DDP. Bioinformatics analysis, dual luciferase reporter gene assay, and RNA pull-down were applied to predict and verify the possible binding relationships. The expressions of FER1L4, E2F transcription factor 1 (E2F1), microRNA-106a-5p (miR-106a-5p), or miR-372-5p were altered in the cells, followed by flow cytometry, Cell Counting Kit-8 (CCK-8), and Transwell assays to evaluate apoptotic, proliferative, and invasive abilities in vitro and nude mice xenografts to observe tumor growth in vivo. FER1L4 was highly expressed and miR-106-5p and miR-372-5p were poorly expressed in tumor cells and tissues. FER1L4 knockdown or the overexpression of miR-106-5p and miR-372-5p inhibited the cancerous cell proliferation and invasion while promoting apoptosis. FERIL4 silencing increased the miR-106-5p/miR-372-5p expression to inhibit the E2F1-activated nuclear factor κB (NF-κB) pathway. Besides, overexpressing FER1L4 led to an increased tumor growth in nude mice, which was reversed by the NF-κB inhibitor pyrollidine dithiocarbamate (PDTC). In conclusion, the results indicated that FER1L4 could inhibit the expression of miR-106a-5p/miR-372-5p, to activate E2F1-mediated NF-κB pathway, leading to drug resistance in liver cancer.