Guidong Yao1,2, Yue Kong3,4, Guang Yang3,4, Deqi Kong3,4, Yijiang Xu3,4, Jiahuan He3,4, Ziwen Xu3,4, Yucheng Bai3,4, Huiying Fan3,4, Qina He3,4, Yingpu Sun5,6. 1. Center for Reproductive Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. ygdzzu@163.com. 2. Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. ygdzzu@163.com. 3. Center for Reproductive Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 4. Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. 5. Center for Reproductive Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. syp2008@vip.sina.com. 6. Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. syp2008@vip.sina.com.
Abstract
BACKGROUNDS: Long non-coding RNA is a novel group of non-protein coding transcripts over 200 nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. RESULTS: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1-2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1-2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. CONCLUSIONS: Lnc-GULP1-2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.
BACKGROUNDS: Long non-coding RNA is a novel group of non-protein coding transcripts over 200 nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. RESULTS: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1-2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1-2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. CONCLUSIONS: Lnc-GULP1-2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.
Authors: Thomas Derrien; Rory Johnson; Giovanni Bussotti; Andrea Tanzer; Sarah Djebali; Hagen Tilgner; Gregory Guernec; David Martin; Angelika Merkel; David G Knowles; Julien Lagarde; Lavanya Veeravalli; Xiaoan Ruan; Yijun Ruan; Timo Lassmann; Piero Carninci; James B Brown; Leonard Lipovich; Jose M Gonzalez; Mark Thomas; Carrie A Davis; Ramin Shiekhattar; Thomas R Gingeras; Tim J Hubbard; Cedric Notredame; Jennifer Harrow; Roderic Guigó Journal: Genome Res Date: 2012-09 Impact factor: 9.043
Authors: Said Assou; Delphine Haouzi; Hervé Dechaud; Anna Gala; Alice Ferrières; Samir Hamamah Journal: Biomed Res Int Date: 2013-09-12 Impact factor: 3.411