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hsa_circ_001946 elevates HOXA10 expression and promotes the development of endometrial receptivity via sponging
Fang Zhao1, Yihong Guo2, Zhanrong Shi3
1Department of Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University, Νo. 1 Jianshe East Road, Henan, 450000, Zhengzhou, PR China.
Insights
Hsa_circ_001946 enhances endometrial receptivity by promoting cell proliferation and decidualization. It achieves this by sponging miR-135b, which in turn elevates HOXA10 expression, crucial for embryo implantation.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Impaired endometrial receptivity is a primary cause of embryo implantation failure.
- The role of circular RNAs (circRNAs) in endometrial receptivity remains largely unexplored.
- This study investigates the function and mechanism of hsa_circ_001946 in endometrial receptivity.
Purpose of the Study:
- To investigate the role of hsa_circ_001946 in endometrial receptivity.
- To elucidate the underlying molecular mechanisms involving miR-135b and HOXA10.
- To assess the impact of hsa_circ_001946 on cell proliferation, cell cycle, and decidualization.
Main Methods:
- Quantitative RT-PCR (qRT-PCR) to measure expression levels of hsa_circ_001946, miR-135b, and HOXA10 in endometrial tissues.
- Immunohistochemistry (IHC) and western blotting to determine protein levels of HOXA10 and cell cycle markers.
- Dual luciferase reporter assays to confirm binding interactions.
- MTT and FACS assays to evaluate cell proliferation and cell cycle.
- In vitro decidualization of T-HESCs to assess hsa_circ_001946 function on decidual markers (PRL, IGFBP1).
Main Results:
- Patients with recurrent implantation failure exhibited lower hsa_circ_001946 and HOXA10 expression, and higher miR-135b expression.
- Hsa_circ_001946 acts as a sponge for miR-135b, thereby promoting HOXA10 expression.
- Overexpression of hsa_circ_001946 restored cell proliferation and cell cycle progression.
- Decidualized cells showed increased hsa_circ_001946 and HOXA10, with decreased miR-135b.
- Hsa_circ_001946 overexpression reversed miR-135b-induced suppression of decidual markers (PRL, IGFBP1).
Conclusions:
- Hsa_circ_001946 enhances endometrial receptivity by promoting cell proliferation and cell cycle progression.
- Hsa_circ_001946 facilitates decidualization by increasing PRL and IGFBP1 expression.
- The mechanism involves sponging miR-135b to elevate HOXA10 levels, ultimately improving endometrial receptivity.
Background:
Impaired endometrial receptivity is a major reason for embryo implantation failure. There's a paucity of information regarding the role of circRNAs on endometrial receptivity. Here, we investigated the function of hsa_circ_001946 on endometrial receptivity and its mechanisms.
Methods:
A total of 50 women composing 25 with recurrent implantation failure and 25 who conceived after their implantation were recruited in this study. Expression of hsa_circ_001946, miR-135b, and HOXA10 was evaluated by quantitative RT-PCR (qRT-PCR) in biopsied endometrial tissue samples. The levels of HOXA10, and cell cycle markers (CCNB1, CDK1, and CCND1) were determined by IHC and western blotting assays. Binding relationship among miR-135b, hsa_circ_001946 and HOXA10 were confirmed by dual luciferase reporter assays and western blotting. MTT assays and cell cycle assays by FACS were employed to evaluate the proliferation and cell cycle of cells. T-HESCs were cultured with 1 µM medroxyprogesterone acetate (MPA) and 0.5 mM 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP) to induce decidualization. The mechanisms and functions of hsa_circ_001946 on decidualization were further assessed by qRT-PCR evaluating the expression of hsa_circ_001946, miR-135b, HOXA10 and decidual markers (PRL and IGFBP1) in T-HESCs.
Results:
Endometrial tissues from patients with recurrent implantation failure had lower hsa_circ_001946 expression, higher miR-135b expression, and lower HOXA10 expression. Hsa_circ_001946 promoted HOXA10 expression by sponging miR-135b in T-HESCs. Overexpression of hsa_circ_001946 restored cell proliferation and cell cycle that were disrupted by miR-135b overexpression in T-HESCs. Decidualized T-HESCs had higher hsa_circ_001946 expression, lower miR-135b expression, and higher HOXA10 expression. Overexpression of hsa_circ_001946 reversed the expression of decidual markers (PRL and IGFBP1) that were suppressed by miR-135b overexpression in T-HESCs.
Conclusions:
In conclusion, our findings suggest that hsa_circ_001946 promotes cell proliferation and cell cycle process and increases expression of decidualization markers to enhance endometrial receptivity progression via sponging miR-135b and elevating HOXA10.
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