LINC00665通过吸附miR-138-5p上调SIN3A表达以调节结直肠癌进展。

LINC00665 up-regulates SIN3A expression to modulate the progression of colorectal cancer via sponging miR-138-5p.

作者信息

Nan Shoushan, Zhang Shuangxia, Jin Rong, Wang Juelei

机构信息

Department of Gastroenterology, Tianjin Fifth Center Hospital, No. 41 Zhejiang Road, Binhai New District, Tianjin, 300450, China.

Department of Gastroenterology, Tianjin First Center Hospital, Tianjin, 300384, China.

出版信息

Cancer Cell Int. 2022 Jan 31;22(1):51. doi: 10.1186/s12935-021-02176-4.

BACKGROUND

Colorectal cancer (CRC) is a malignant tumor affecting people worldwide. Long noncoding RNAs (lncRNAs) is a crucial factor modulating various cancer progression, including CRC. Long intergenic non-protein coding RNA 665 (LINC00665) has been proven as an oncogene in several cancers, but its function in CRC is still unclear.

METHODS

QRT-PCR was performed for RNA quantification. Functional assays were designed and carried to test cell phenotype while mechanism experiments were adopted for detecting the interaction of LINC00665, microRNA-138-5p (miR-138-5p) and SIN3 transcription regulator family member A (SIN3A). In vivo experiments were conducted to test LINC00665 function on modulating CRC tumor progression.

RESULTS

LINC00665 displayed high expression in CRC tissues and cells, and promoted tumor progression in vivo. MiR-138-5p displayed abnormally low expression in CRC, and was verified to be sponged by LINC00665. Furthermore, SIN3A, as the downstream mRNA of miR-138-5p, exerted promoting impacts on CRC cells. Rescue experiments certified that overexpressed SIN3A or silenced miR-138-5p could offset the repressed function of LINC00665 knockdown on CRC progression.

CONCLUSIONS

LINC00665 could sponge miR-138-5p to up-regulate SIN3A expression, thus accelerating CRC progression.

背景

结直肠癌（CRC）是一种影响全球人群的恶性肿瘤。长链非编码RNA（lncRNAs）是调节包括CRC在内的各种癌症进展的关键因素。长链基因间非编码RNA 665（LINC00665）已被证实在多种癌症中是一种癌基因，但其在CRC中的功能仍不清楚。

方法

进行QRT-PCR以定量RNA。设计并进行功能试验以检测细胞表型，同时采用机制实验检测LINC00665、微小RNA-138-5p（miR-138-5p）和SIN3转录调节因子家族成员A（SIN3A）之间的相互作用。进行体内实验以测试LINC00665对调节CRC肿瘤进展的功能。

结果

LINC00665在CRC组织和细胞中高表达，并在体内促进肿瘤进展。miR-138-5p在CRC中表达异常低，并被证实被LINC00665吸附。此外，SIN3A作为miR-138-5p的下游mRNA，对CRC细胞有促进作用。挽救实验证实，过表达SIN3A或沉默miR-138-5p可抵消LINC00665敲低对CRC进展的抑制作用。