长链非编码 RNA TUSC7 通过靶向 miR-616 调控 SOCS4（SOCS5）表达抑制子宫内膜癌细胞增殖、迁移和侵袭。

Long noncoding RNA TUSC7 inhibits cell proliferation, migration and invasion by regulating SOCS4 (SOCS5) expression through targeting miR-616 in endometrial carcinoma.

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.

出版信息

Life Sci. 2019 Aug 15;231:116549. doi: 10.1016/j.lfs.2019.116549. Epub 2019 Jun 12.

DOI:10.1016/j.lfs.2019.116549

PMID:31200002

Abstract

BACKGROUND

Long non-coding RNA (lncRNA) is emerging as an important regulator in various physiological and pathological processes. Recently, it was found that lncRNA long non-coding RNA tumor suppressor candidate 7 (TUSC7) could play tumor suppressive roles in several cancers. However, the function and underlying regulatory mechanism of lncRNA TUSC7 in endometrial carcinoma (EC) remains largely unclear.

METHODS

The expression levels of TUSC7 and microRNAs-616 (miR-616) were analyzed by real-time PCR and in situ hybridization. Cell cycle and cell metastasis associated protein expressions were determined by western blotting. Cell proliferation, cycle and metastasis were determined by CCK-8 cell viability, colony formation, flow cytometer, wound scratch and transwell assays respectively in vitro. RNA pull-down, luciferase and western blotting assays were used to examine the target relationship between TUSC7 and miR-616 or that between miR-616 and suppressors of cytokine signaling 4 (5) (SOCS4 (SOCS5)). The functional effects of TUSC7 through sponging miR-616 were further examined using a xenograft tumor mouse model in vivo.

RESULTS

TUSC7 was downexpressed in EC tissues and cell lines, and TUSC7 upregulation could remarkably inhibit cell proliferation, cycle progression and metastasis in EC cells. Mechanistic investigations demonstrated that TUSC7 can interact with miR-616 and decrease its expression, thereby upregulating the expression of miR-616's targets SOCS4 (SOCS5). Additionally, in vivo experiments using a xenograft tumor mouse model revealed that TUSC7 can serve as a tumor suppressor through sponging miR-616, and upregulating SOCS4 (SOCS5) in EC.

CONCLUSIONS

In this study, a newly identified regulatory mechanism of lncRNA TUSC7/miR-616/ SOCS4 (SOCS5) axis was systematically studied, which may hold promise as a promising target for EC treatment.

摘要

背景

长链非编码 RNA（lncRNA）在各种生理和病理过程中作为重要的调节剂而出现。最近发现，长非编码 RNA 肿瘤抑制候选物 7（TUSC7）在几种癌症中可以发挥肿瘤抑制作用。然而，lncRNA TUSC7 在子宫内膜癌（EC）中的功能和潜在调节机制在很大程度上仍不清楚。

方法

通过实时 PCR 和原位杂交分析 TUSC7 和 microRNAs-616（miR-616）的表达水平。通过 Western blot 测定细胞周期和细胞转移相关蛋白的表达。通过 CCK-8 细胞活力、集落形成、流式细胞仪、划痕和 Transwell 测定分别在体外测定细胞增殖、周期和转移。使用 RNA 下拉、荧光素酶和 Western blot 测定来检查 TUSC7 与 miR-616 或 miR-616 与细胞因子信号转导 4（SOCS4（SOCS5））之间的靶关系。通过体内异种移植肿瘤小鼠模型进一步研究 TUSC7 通过海绵 miR-616 的功能影响。

结果

TUSC7 在 EC 组织和细胞系中表达下调，TUSC7 上调可显著抑制 EC 细胞的增殖、周期进展和转移。机制研究表明，TUSC7 可与 miR-616 相互作用并降低其表达，从而上调 miR-616 靶 SOCS4（SOCS5）的表达。此外，使用异种移植肿瘤小鼠模型的体内实验表明，TUSC7 可通过海绵 miR-616 并上调 EC 中的 SOCS4（SOCS5）发挥肿瘤抑制作用。