MIR4435-2HG, miR-125b-5p, and Sema4D axis affects the aggressiveness of colorectal cancer cells.

INTRODUCTION: The purpose of this study is to elucidate the impact of long non-coding RNA (lncRNA) MIR4435-2HG/microRNA (miR)-125b-5p/ Semaphorins 4D (Sema4D) on colorectal cancer (CRC) cell propagation and migration.

MATERIAL AND METHODS: Sema4D expression in 73 pairs of CRC tissues and matched adjacent normal tissues was measured by qRT-PCR and western blot and its association with pathological characteristics of CRC patients was analyzed by chi-square test. Also, the expression of MIR4435-2HG, miR-125b-5p and Sema4D in CRC cell lines was detected by qRT-PCR and Western blot. Knockdown or overexpression of MIR4435-2HG, miR-125b- 5p and Sema4D were separately performed in Caco-2 and LoVo cells, and the cell propagation, migration and invasiveness were detected by cell-counting kit 8, scratch, and transwell assays.

RESULTS: LncRNA MIR4435-2HG and Sema4D were highly expressed, while miR-125b-5p expression was decreased in CRC tissues and cells. Knockdown of MIR4435-2HG/Sema4D or overexpression of miR-125b-5p inhibited CRC cell proliferation and aggressiveness; overexpression of MIR4435-2HG/Sema4D or knockdown of miR-125b-5p prompted the malignant behaviors of cancer cells. MIR4435-2HG and Sema4D competitively bound to miR-125b-5p.

CONCLUSIONS: LncRNA MIR4435-2HG targets miR-125b-5p to upregulate Sema4D expression, and thus regulates CRC cell propagation, migration and invasiveness.