RBBP6 通过靶向 PIK3R6 加剧卵巢癌的进展。

RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6.

机构信息

Department of Clinical Laboratory, Heze Center for Disease Control and Prevention, Heze, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10366-10374. doi: 10.26355/eurrev_202010_23386.

DOI:10.26355/eurrev_202010_23386

PMID:33155192

Abstract

OBJECTIVE

RBBP6 is identified to be a cancer-associated gene by bioinformatics analysis. This study aims to explore the role of RBBP6 in regulating proliferation and metastasis in ovarian cancer, thus providing theoretical references for ovarian cancer treatment.

PATIENTS AND METHODS

Differential expressions of RBBP6 in ovarian cancer and normal ones were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between RBBP6 and prognosis in ovarian cancer patients was analyzed. The interaction between RBBP6 and PIK3R6 was detected by bioinformatics analysis and Dual-Luciferase reporter assay. Moreover, regulatory effects of RBBP6 and PIK3R6 on proliferative and migratory potentials in A2780 and CAOV3 cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Finally, tumorigenicity assay was conducted in nude mice to illustrate the in vivo regulations of PBBP6 and PIK3R6 on ovarian cancer growth.

RESULTS

RBBP6 was upregulated in ovarian cancer tissues than normal ones. RBBP6 was irrelevant to age, tumor size and tumor node metastasis (TNM) staging in ovarian cancer patients, but correlated to lymphatic metastasis and distant metastasis. RBBP6 was abundantly expressed in ovarian cancer cells, and among the tested cell lines, CAOV3 and A2780 expressed the highest level of RBBP6. Knockdown of RBBP6 attenuated in vitro proliferative and migratory potentials in CAOV3 and A2780 cells. PIK3R6 was the target gene binding RBBP6, which was positively regulated by RBBP6. Overexpression of PIK3R6 could abolish the inhibited proliferative and migratory potentials in ovarian cancer cells with RBBP6 knockdown. In addition, the knockdown of RBBP6 slowed the in vivo growth of ovarian cancer in nude mice, and the alleviated cancer progression was reversed by overexpression of PIK3R6.

CONCLUSIONS

RBBP6 is highly expressed in ovarian cancer cases, which stimulates proliferative and migratory potentials by targeting PIK3R6. RBBP6 may be a novel therapeutic target for ovarian cancer.

摘要

目的

通过生物信息学分析，发现 RBBP6 是一种与癌症相关的基因。本研究旨在探讨 RBBP6 对卵巢癌增殖和转移的调控作用，为卵巢癌的治疗提供理论依据。

方法

采用实时定量聚合酶链反应（qRT-PCR）检测卵巢癌和正常组织中 RBBP6 的差异表达。分析 RBBP6 与卵巢癌患者预后的关系。通过生物信息学分析和双荧光素酶报告基因检测分析 RBBP6 与 PIK3R6 的相互作用。此外，通过细胞计数试剂盒-8（CCK-8）和 Transwell 实验分别检测 RBBP6 和 PIK3R6 对 A2780 和 CAOV3 细胞增殖和迁移能力的调节作用。最后，在裸鼠体内进行肿瘤生成实验，以阐明 RBBP6 和 PIK3R6 对卵巢癌生长的体内调节作用。

结果

RBBP6 在卵巢癌组织中的表达高于正常组织。RBBP6 与卵巢癌患者的年龄、肿瘤大小和肿瘤淋巴结转移（TNM）分期无关，但与淋巴转移和远处转移有关。RBBP6 在卵巢癌细胞中大量表达，在测试的细胞系中，CAOV3 和 A2780 细胞中 RBBP6 的表达水平最高。RBBP6 敲低可减弱 CAOV3 和 A2780 细胞的体外增殖和迁移能力。PIK3R6 是与 RBBP6 结合的靶基因，其受 RBBP6 的正向调节。过表达 PIK3R6 可消除 RBBP6 敲低后卵巢癌细胞增殖和迁移能力的抑制作用。此外，RBBP6 敲低可减缓裸鼠体内卵巢癌的生长，而过表达 PIK3R6 则可逆转这种减轻的癌症进展。