Sun Weixuan, Nie Wenting, Wang Zhaoyi, Zhang Haolong, Li Yezhou, Fang Xuedong
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
Onco Targets Ther. 2020 Jun 22;13:5913-5925. doi: 10.2147/OTT.S246092. eCollection 2020.
BACKGROUND/AIM: LncRNA plays a key role in tumor progression. HAGLR functions as an oncogene in many cancers. However, the molecular mechanism of HAGLR in colon cancer is still unclear.
qRT-PCR was used to measure the expression of HAGLR, miR-185-5p in colon cancer. The expression of CDK4 and CDK6 was detected by Western blot. CCK-8 assay, EdU staining, transwell and Annexin V-FITC/PI assay were used to analyze the effect of HAGLR and miR-185-5p on cell proliferation, invasion, migration and apoptosis. Bioinformatic analysis and luciferase were used to analyze the target genes of HAGLR and miR-185-5p. Nude mice were used to detect mouse tumor changes.
Compared with normal colon cancer tissues and cells, the expression of HAGLR was increased in colon cancer tissues and cells. In addition, the expression of HAGLR down-regulation inhibited the growth, migration, and invasion of colon cancer cells. MiR-185-5p was reduced in colon cancer, and CDK4 and CDK6 acted as target genes of miR-185-5p to regulate the progress of colon cancer. And CDK4 and CDK6 were predicted as downstream targets of miR-185-5p. Finally, it was demonstrated that HAGLR regulated tumor progression in vivo.
Lnc HAGLR promoted the development of colon cancer by miR-185-5p/CDK4/CDK6 axis, and lnc HAGLR might be potential target for colon cancer.
背景/目的：长链非编码RNA（lncRNA）在肿瘤进展中起关键作用。HAGLR在多种癌症中作为癌基因发挥作用。然而，HAGLR在结肠癌中的分子机制仍不清楚。
采用qRT-PCR检测结肠癌中HAGLR、miR-185-5p的表达。通过蛋白质免疫印迹法检测细胞周期蛋白依赖性激酶4（CDK4）和细胞周期蛋白依赖性激酶6（CDK6）的表达。采用细胞增殖-毒性检测（CCK-8）实验、5-乙炔基-2'-脱氧尿苷（EdU）染色、Transwell实验和膜联蛋白V-异硫氰酸荧光素/碘化丙啶（Annexin V-FITC/PI）检测法分析HAGLR和miR-185-5p对细胞增殖、侵袭、迁移和凋亡的影响。利用生物信息学分析和荧光素酶检测分析HAGLR和miR-185-5p的靶基因。使用裸鼠检测小鼠肿瘤变化。
与正常结肠癌组织和细胞相比，结肠癌组织和细胞中HAGLR的表达增加。此外，HAGLR表达下调抑制了结肠癌细胞的生长、迁移和侵袭。miR-185-5p在结肠癌中表达降低，CDK4和CDK6作为miR-185-5p的靶基因调节结肠癌进展。并且CDK4和CDK6被预测为miR-185-5p的下游靶标。最后，证实HAGLR在体内调节肿瘤进展。
lncRNA HAGLR通过miR-185-5p/CDK4/CDK6轴促进结肠癌的发展，lncRNA HAGLR可能是结肠癌的潜在治疗靶点。
