Linc01559 Served as a Potential Oncogene and Promoted Resistance of Hepatocellular Carcinoma to Oxaliplatin by Directly Sponging miR-6783-3p

Background: Oxaliplatin (L-OHP)-based chemotherapy, such as FOLFOX4 (5-fluorouracil, leucovorin, and L-OHP), improves the prognosis of patients with late-stage Hepatocellular Carcinoma (HCC). However, the development of resistance to L-OHP leads to the failure of chemotherapy. The aim of this study was to investigate the role of linc01559 and miR-6783-3p in regulating resistance to L-OHP.

Methods: Quantitative reverse transcription-polymerase chain reaction was used to determine the expression profile. The Cell Counting Kit-8 test and wound healing assay were also used. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation were used to evaluate the interaction between linc01559 and miR-6783-3p.

Result: linc01559 expression was associated with response to FOLFOX4, as well as miR-1343-3p and miR- 6783-3p expression in vivo. A nomogram, including linc01559 and miR-1343-3p, precisely and accurately predicted the overall survival of patients with HCC. Regarding the in vitro tests, linc01559 showed higher expression in L-OHP-resistant cell lines, whereas miR-6783-3p was downregulated. Knockdown of linc01559 led to decreased proliferation and migration ability, and increased expression of miR-6783-3p; however, it did not influence the expression of miR-1343-3p. We also found that linc01559 directly interacted with miR-6783-3p. Furthermore, linc01559 and miR-6783-3p regulated the viability of L-OHP-resistant cells following treatment with L-OHP.

Conclusion: linc01559 promoted the proliferation of HCC by sponging miR-6783-3p. This suggests that linc01559/miR-6783-3p may be key factors in regulating resistance and response to L-OHP. Moreover, they may be potential therapeutic targets for improving sensitivity to L-OHP in patients with HCC.