lncRNA GCAT1 is involved in premature ovarian insufficiency by regulating p27 translation in GCs via competitive binding to PTBP1

Li, Duan; Wang, Xiaoyan; Dang, Yujie; Zhang, Xinyue; Zhao, Shidou; Lü, Gang; Chan, Wai‐Yee; Leung, Peter C.K.; Qin, Yingying

doi:10.1016/j.omtn.2020.10.041

Cited by 23 publications

(15 citation statements)

References 37 publications

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“…In the present study, we showed that down-regulated lncRNA ZNF674-AS1 significantly inhibited the proliferation of GCs. Similarly, lncRNA GCAT1 has been shown to regulate GCs proliferation in patients with bPOI 25 . Our study provided new regulatory evidence conducted by lncRNA that mediates GCs proliferation.…”

Section: Discussionmentioning

confidence: 98%

LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA

Wang

et al. 2021

Cell Death Discov.

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Granulosa cell (GC) is a critical somatic component of ovarian follicles to support oocyte development, while the regulatory role of long noncoding RNA (lncRNA) in GCs is largely unknown. Here, we identified a down-regulated lncRNA ZNF674-AS1 in GCs from patients with biochemical premature ovarian insufficiency (bPOI), and its expression correlates with serum levels of clinical ovarian reserve indicators. Functional experiments showed that ZNF674-AS1 is induced by energy stress, and regulates the proliferation and glycolysis of GCs, which possibly leads to follicular dysfunction. Mechanistically, low-expressed ZNF674-AS1 reduced the enzymatic activity of aldolase A (ALDOA), concomitant with promoting the association between ALDOA and v-ATPase to activate the lysosome localized AMP-activated protein kinase (AMPK). These findings identified a new lncRNA–ALDOA complex through which ZNF674-AS1 exerts its functions, expanding the understanding of epigenetic regulation of GCs function and POI pathogenesis.

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Section: Discussionmentioning

confidence: 98%

LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA

Wang

et al. 2021

Cell Death Discov.

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“…The discrepancies between the DE lncRNAs identi ed in our study and those in other studies are due (at least in part) to differences in sample selection and sequencing methods. Moreover, several researchers have conducted functional studies on these DE lncRNAs (33)(34)(35) and reported different underlying molecular mechanisms. However, most of those studies concentrated on a particular gene or signaling pathway and did not analyze them from a holistic perspective.…”

Section: Discussionmentioning

confidence: 99%

Expression of Long Noncoding RNAs in the Ovarian Granulosa Cells of Women with Diminished Ovarian Reserve Using High-Throughput Sequencing

Dong

Xin

Chang

et al. 2022

Preprint

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Background: Infertility is a global reproductive-health problem, and diminished ovarian reserve (DOR) is one of the common causes of female infertility. Long noncoding RNAs (lncRNAs) are crucial regulators of numerous physiological and pathological processes in humans. However, whether lncRNAs are involved in the development of DOR remains to be elucidated. Methods: Ovarian granulosa cells (OGCs) extracted from infertile women with DOR and from women with normal ovarian reserve (NOR) were subjected to high-throughput sequencing. Comprehensive bioinformatics analysis was conducted to identify the differential expression of messenger RNAs (mRNAs) and lncRNAs. Sequencing results were validated by the selection of random lncRNAs using real-time reverse transcription-quantitative polymerase chain reaction.Results: Compared with the NOR group, a total of 244 lncRNAs were upregulated (53 known and 191 novel), and 222 lncRNAs were downregulated (36 known and 186 novel) in the DOR group. Similarly, 457 mRNAs had differential expression between the two groups. Of these, 169 were upregulated and 288 were downregulated. Bioinformatics analysis revealed that the differentially expressed genes of mRNA and lncRNAs were considerably enriched in “cell adhesion and apoptosis”, “steroid biosynthesis”, and “immune system”. A co-expression network comprising lncRNAs and their predicted target genes revealed the possible involvement of the “thyroid hormone signaling pathway” and “protein binding, digestion and absorption” in DOR pathogenesis. The expression of SLC16A10 was positively regulated by multiple lncRNAs. Seven differentially expressed lncRNAs (NEAT1, RAB5A, MEG3, GNG12, MST1L, GCN1, and ZEB2-AS1) were identified, among which the expression of NEAT1, GNG12 and ZEB2-AS1 was in accordance with RNA-sequencing. Conclusions: We presented the first data showing that the expression profiles of lncRNA and mRNA in OGCs between NOR and DOR patients using RNA sequencing. The lncRNAs that we identified may serve as novel diagnostic biomarkers or drug targets for patients with DOR.

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“…Granulosa cells (GCs) dysfunction causes follicular atresia and has been implicated as the main cause of premature ovarian insufficiency (POI) 49 . Duan et al found that lncRNA LINC02690 or GCAT1 (granulosa cell-associated transcript 1) is down regulated in the GCs of patients with biochemical POI (bPOI), which is demonstrated as a novel form of lncRNA-mediated epigenetic regulation of GC function that contributes to the pathogenesis of POI 50 . Studies have shown that stem cells from different sources play an important role in ovarian recovery through multiple mechanisms such as migration, anti-apoptosis, anti-fibrosis, angiogenesis, anti-inflammatory, immune regulation, and oxidative stress.…”

Section: Human Infertility Defectsmentioning

confidence: 99%

Stem Cell Therapies for Human Infertility: Advantages and Challenges

Xia

She

et al. 2022

Cell Transplant

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Physical and mental health and hormonal imbalance are associated with the problems related to infertility and reproductive disorders. The rate of infertility has increased globally over the years, due to various reasons. Given the psychosocial implications of infertility and its effects on the life of the affected people, there has been an increased focus on its treatment over the last several years. Assisted reproductive technology can only solve about 50% of the cases. Moreover, it contains significant risks and does not solve the fundamental problem of infertility. As pluripotent stem cells have the potential to differentiate into almost any type of cell, they have been widely regarded as a promising option in the development of stem cell-based fertility treatments, which could even correct genetic diseases in offspring. These advancements in reproductive biotechnology present both challenges and possibilities for solving infertility problems caused by various unexplainable factors. This review briefly presents the different types of infertility disorders and the potential applications of stem cells in the treatment of these reproductive diseases.

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lncRNA GCAT1 is involved in premature ovarian insufficiency by regulating p27 translation in GCs via competitive binding to PTBP1

Cited by 23 publications

References 37 publications

LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA

LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA

Expression of Long Noncoding RNAs in the Ovarian Granulosa Cells of Women with Diminished Ovarian Reserve Using High-Throughput Sequencing

Stem Cell Therapies for Human Infertility: Advantages and Challenges

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