Knockdown of LINC00473 Enhances Radiosensitivity in Hepatocellular Carcinoma via Regulating the miR-345-5p/FOXP1 Axis

Abstract

Background

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Radioresistance is a significant obstacle in HCC therapy. Long non-coding RNA 473 (LINC00473) has been found to impair the effect of radiotherapy. This study aimed to explore the function and molecular basis of LINC00473 in the radiosensitivity of HCC cells.

Methods

The levels of LINC00473, miR-345-5p and Forkhead Box P1 (FOXP1) were determined by quantitative real-time polymerase chain reaction. Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Survival fraction was calculated by colony survival assay after exposure to different doses of radiation. Cell apoptosis was evaluated by flow cytometry. The interaction among LINC00473, miR-345-5p and FOXP1 was confirmed by dual-luciferase reporter assay. The protein level of FOXP1 was detected by Western blot assay.

Results

LINC00473 and FOXP1 were up-regulated, while miR-345-5p was down-regulated in HCC tissues and cells. Radiation elevated LINC00473 expression in a dose- and time-dependent manner. Depletion of LINC00473 inhibited proliferation and heightened radiosensitivity and apoptosis in HCC cells. In addition, LINC00473 was a sponge of miR-345-5p. Also, miR-345-5p overexpression sensitized HCC cells to radiation. Moreover, miR-345-5p directly targeted FOXP1. MiR-345-5p inhibition or FOXP1 up-regulation reversed the enhanced radiosensitivity caused by LINC00473 knockdown.

Conclusion

LINC00473 contributed to radioresistance in HCC via modulating the miR-345-5p/FOXP1 axis, which might provide a promising diagnostic marker for HCC radiotherapy.