长链非编码 RNA RBAT1 通过海绵吸附 miR-27b 降低子宫内膜癌细胞对卡铂/紫杉醇的化疗敏感性。

LncRNA RBAT1 reduces chemosensitivity of cancer cells to carboplatin/paclitaxel by sponging miR‑27b in endometrial carcinoma.

机构信息

Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, 646000, P.R. China.

Sichuan Treatment Center for Gynaecologic and Breast Diseases (Gynaecology), Luzhou City, Sichuan Province, 646000, P.R. China.

出版信息

J Ovarian Res. 2023 Jul 27;16(1):147. doi: 10.1186/s13048-023-01235-w.

DOI:10.1186/s13048-023-01235-w

PMID:37501162

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10375650/

Abstract

BACKGROUND

A recent study reported the role of long non-coding RNA (lncRNA) RBAT1 in promoting the development of retinoblastoma and bladder cancer. However, its function in other cancers is unclear. We then studied the role of RBAT1 in endometrial carcinoma (EC).

METHODS

The expression of RBAT1 and miR-27b in EC and paired non-tumor samples from advanced EC patients, as well as in plasma samples of EC patients and healthy controls were detected by RT-qPCR. The direct interaction between RBAT1 and miR-27b, and the subcellular location of RBAT1 were determined by RNA-RNA pulldown assay and subcellular fractionation assay, respectively.

RESULTS

EC tissues showed increased expression levels of RBAT1 and decreased expression levels of miR-27b compared to that in non-tumor tissues. Moreover, EC patients showed higher plasma expression levels of RBAT1 and lower plasma expression levels of miR-27b compared to that in the controls. Drug-resistant (DR) patients showed higher expression levels of RBAT1 and lower expression levels of miR-27b in both EC tissues and plasma samples. RBAT1 was detected in both nuclear and cytoplasm and it directly interacted with miR-27b. RBAT1 and miR-27b did not affect the expression of each other. Upregulation of RBAT1 promoted the expression of multidrug-resistant-related protein (P-gp, MRP1, and BCRP). Overexpression of RBAT1 and inhibition of miR-27b promoted cell viability and impeded cell apoptosis and cell cycle arrest at G0-G1 phase, while knockdown of RBAT1 and overexpression of miR-27b inhibited cell viability and induced cell apoptosis and cell cycle arrest at G0-G1 phase. Moreover, miR-27b could abolish RBAT1-induced effects on cell viability, apoptosis and cell cycle.

CONCLUSION

RBAT1 may reduce the chemosensitivity of EC cells to carboplatin/paclitaxel by sponging miR-27b in EC.

摘要

背景

最近的一项研究报道了长非编码 RNA（lncRNA）RBAT1 在促进视网膜母细胞瘤和膀胱癌发展中的作用。然而，其在其他癌症中的功能尚不清楚。我们随后研究了 RBAT1 在子宫内膜癌（EC）中的作用。

方法

通过 RT-qPCR 检测 RBAT1 和 miR-27b 在 EC 及晚期 EC 患者配对非肿瘤样本中的表达，以及在 EC 患者和健康对照者的血浆样本中的表达。通过 RNA-RNA 下拉实验和亚细胞分离实验分别确定 RBAT1 与 miR-27b 的直接相互作用和 RBAT1 的亚细胞定位。

结果

与非肿瘤组织相比，EC 组织中 RBAT1 的表达水平升高，miR-27b 的表达水平降低。此外，与对照组相比，EC 患者的血浆中 RBAT1 的表达水平较高，miR-27b 的表达水平较低。耐药（DR）患者的 EC 组织和血浆样本中，RBAT1 的表达水平较高，miR-27b 的表达水平较低。RBAT1 被检测到存在于核和细胞质中，并且可以直接与 miR-27b 相互作用。RBAT1 和 miR-27b 不会影响彼此的表达。RBAT1 的上调促进了多药耐药相关蛋白（P-gp、MRP1 和 BCRP）的表达。RBAT1 的过表达和 miR-27b 的抑制促进了细胞活力，并阻碍了细胞凋亡和 G0-G1 期的细胞周期停滞，而 RBAT1 的敲低和 miR-27b 的过表达则抑制了细胞活力，并诱导了 G0-G1 期的细胞凋亡和细胞周期停滞。此外，miR-27b 可以消除 RBAT1 对细胞活力、凋亡和细胞周期的诱导作用。