lncRNA LINC00963通过靶向miR-148b-3p对结直肠癌细胞增殖、迁移和侵袭的影响研究

Effects of lncRNA LINC00963 on the proliferation,migration,and invasion of colorectal cancer cells by targeting miR-148b-3p

结直肠癌(CRC)是全球性最常见的恶性肿瘤。前期实验表明,低氧环境下的CRC细胞分泌的外泌体中长链非编码RNA核富集转录体1(LncRNA NEAT1)的表达水平明显较高。低氧环境下培养48 h后CRC细胞(HCT116和SW480)分泌的外泌体中,通过高通量转录组测序发现了一种功能未知的LncRNA NEAT1,在低氧环境中HCT116和SW480分泌的外泌体中含量显著上调。将定制的LncRNA NEAT1 mimic体外处理正常条件培养的HCT116和SW480细胞,发现LncRNA NEAT1 mimic处理显著促进了HCT116和SW480细胞的增殖和迁移。本次研究显示,与Si-LINC00963+anti-miR-NC组相比,Si-LINC00963+anti-miR-148b-3p组的miR-148b-3p表达水平降低,迁移和侵袭细胞数增加(P<0.05)。表明miR-148b-3p受LINC00963的靶向调控,并且抑制miR-148b-3p表达能逆转干扰LINC00963对HT29细胞的作用。本研究为CRC的早期诊断、靶向治疗提供新的分子靶标,为CRC诊疗的临床转化提供临床前研究基础。

Colorectal cancer(CRC)is the most common malignant tumor worldwide.Previous experiments have shown that in the exosomes secreted by CRC cells under hypoxic conditions,long non-coding RNA nuclear enriched abundant transcript 1(LncRNA NEAT1)has a significantly higher expression level.An LncRNA NEAT1 of unknown function has been identified by high-throughput transcriptome sequencing in exosomes secreted by CRC cells(HCT116 and SW480)after 48 h of incubation in a hypoxic environment,and its content was significantly up-regulated in exosomes secreted by HCT116 and SW480 in a hypoxic environment.The customized LncRNA NEAT1 mimic was used to treat HCT116 and SW480 cells cultured under normal conditions in vitro,and it was found that LncRNA NEAT1 mimic treatment significantly promoted the proliferation and migration of HCT116 and SW480 cells.The current study has showed that the Si-LINC00963+anti-miR-NC group had a decreased expression level of miR-148b-3p and an increased number of migrating and invasive cells compared with the Si-LINC00963+anti-miR-NC group(P<0.05).It indicated that miR-148b-3p was targetregulated by LINC00963 and that inhibition of miR-148b-3p expression reversed the effects of interfering with LINC00963 on HT29 cells.This study provides new molecular targets for early diagnosis and targeted therapy of CRC,and provides a preclinical research basis for the clinical translation of CRC diagnosis and treatment.