Testis-enriched circular RNA circ-Bbs9 plays an important role in Leydig cell proliferation by regulating a CyclinD2-dependent pathway

被引:9
作者
Jia, Minzhi [1 ]
Li, Xiaoliang [1 ]
Jiang, Chuan [1 ]
Wang, Ke [1 ]
Zuo, Tao [1 ]
He, Guolin [2 ]
Qin, Lang [2 ,3 ]
Xu, Wenming [1 ,2 ]
机构
[1] Sichuan Univ, West China Univ Hosp 2, Joint Lab Reprod Med,Minist Educ, SCU CUHK,Key Lab Obstetr Gynaecol & Paediat Dis &, Chengdu 610041, Peoples R China
[2] Sichuan Univ, West China Univ Hosp 2, Dept Obstet & Gynaecol, Chengdu 610041, Peoples R China
[3] Sichuan Univ, West China Univ Hosp 2, Reprod Med Ctr, Dept Obstet & Gynecol, Chengdu 610041, Peoples R China
关键词
cell cycle; cyclin D2; Leydig cell; proliferation; BBS9; GENE;
D O I
10.1071/RD18474
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Circular RNAs belong to a new category of non-coding RNAs, characterised by a circular structure, conservation, stability and high expression in eukaryotes. They often show tissue- or cell-specific expression. Here, we identified a testis-enriched circular RNA (circRNA), circular Bbs9 (circ-Bbs9) that is highly expressed in mouse testis. An RNase R treatment experiment confirmed that circ-Bbs9 is indeed a circRNA. In situ hybridisation experiments showed that circ-Bbs9 is expressed in Leydig cells along seminiferous tubules and in the cytoplasm of the TM3 Leydig cell line. Knocking down the circ-Bbs9 in TM3 cells by lentivirus vectors arrested cell proliferation, whereas overexpression of circ-Bbs9 induced cell proliferation significantly. Knocking down circ-Bbs9 inhibited the protein level of cyclin D2 (Ccnd2) and RNA immunoprecipitation results showed that circ-Bbs9 interacts with Ccnd2. Our results show that use of the Hedgehog pathway Smoothened Agonist (SAG) HCl and antagonists cyclopamine and gant6 affects the expression levels of Glioma-Associated Oncogene Homolog 1 (Gli1), Ccnd2 and other genes in this pathway. Our research reveals that a Leydig cell-specific circRNA, circ-Bbs9, plays a critical role in Leydig cell proliferation through regulating the levels of cell cycle-related Ccnd2. Thus, our results emphasise the important role of circRNA in the male reproductive system.
引用
收藏
页码:355 / 362
页数:8
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