NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis

Wang, Yao; Pan, Zengxiang; Du, Xiaohong; Zhang, Jinbi; Liu, Honglin; Li, Qifa

doi:10.1186/s40104-021-00626-7

Cited by 23 publications

(40 citation statements)

References 66 publications

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“…We performed a subcellular localization assay by separating nuclear and cytoplasmic RNA and showed that miR-23a is more enriched in the nucleus than it is in the cytoplasm of pGCs ( Figure 2 A), indicating that miR-23a induces pGC apoptosis, possibly via an RNAa mechanism. Interestingly, an MRE motif was detected in the promoter region of the porcine NORHA , a pro-apoptotic lncRNA in pGCs ( Figure 2 B), when we previously analyzed its promoter sequence [ 19 ]. Furthermore, the two have a strong potential interaction ability with the -20 kcal/mol of the minimum free energy (MFE) ( Figure 2 C), so NORHA was selected for further investigation.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study demonstrated that FoxO1 , an effector for oxidative stress, is downstream of NORHA in pGCs [ 19 ]. Western blotting showed that the overexpression of miR-23a significantly induces the FoxO1 protein level in pGCs ( Figure 6 A).…”

Section: Resultsmentioning

confidence: 99%

“…lncRNAs and miRNAs are the two most studied endogenous non-coding RNAs (ncRNAs), which form a complex regulatory network with protein-coding genes through various forms of dialogue mechanisms to control health and disease. LncRNAs, for instance, (i) act as a molecular sponge of miRNAs [ 19 ], (ii) compete for protein-coding genes with miRNAs [ 33 ], (iii) act as a precursor or host of miRNAs [ 34 ], and (iv) contribute to miRNA biogenesis [ 35 ]. Meanwhile, miRNAs also inhibit lncRNA expression via an RNAi mechanism, just as they inhibit the 3′-UTRs of protein-encoding genes [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…First, 3~5 mm (diameter) of healthy follicles were used to collect pGCs, and the pGCs were obtained and cultured, as mentioned earlier [ 19 ]. After 12 h of culture, DNA plasmids, miR-23a mimics, and an miR-23a inhibitor were transfected for a subsequent apoptosis assay, qRT-PCR, chromatin immunoprecipitation (ChIP), and a western blot assay by using HighGene (RM09014, ABclonal, Wuhan, China) according to the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

“…The overexpression plasmids pcDNA3.1- SMAD4 and pcDNA3.1- NORHA were previously constructed [ 19 , 20 ]. For the plasmid pcDNA3.1- NR2C1 , the coding sequence (CDS) region of NR2C1 was amplified from the cDNA of pGCs by using primers containing enzymatic digestion sites and cloned into a pcDNA3.1-basic vector (Promega, Madison, WI, USA).…”

Section: Methodsmentioning

confidence: 99%

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A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress

Wang

Zeng

et al. 2022

Antioxidants

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Phenotypes are the result of the interaction between the gene and the environment, so the response of individuals with different genotypes to an environment is variable. Here, we reported that a mutation in miR-23a influences granulosa cells (GCs) response to oxidative stress, a common mechanism of environmental factors affecting female reproduction. We showed that nuclear miR-23a is a pro-apoptotic miRNA in porcine GCs through the activation of the transcription and function of NORHA, a long non-coding RNA (lncRNA) induces GC apoptosis and responses to oxidative stress. Mechanistically, miR-23a acts as an endogenous small activating RNA (saRNA) to alter histone modifications of the NORHA promoter through the direct binding to its core promoter. A C > T mutation was identified at −398 nt of the miR-23a core promoter, which created a novel binding site for the transcription factor SMAD4 and recruited the transcription repressor SMAD4 to inhibit miR-23a transcription and function in GCs. Notably, g.−398C > T mutation in the miR-23a promoter reduced GCs response to oxidative stress. In addition, g.−398C > T mutation was significantly associated with sow fertility traits. In short, our findings preliminarily revealed the genetic basis of individual differences in the response to oxidative stress from the perspective of a single mutation and identified miR-23a as a candidate gene for the environmental adaptation to oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress

Wang

Zeng

et al. 2022

Antioxidants

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A Mutation Losing an RBP‐Binding Site in the LncRNA NORSF Transcript Influences Granulosa Cell Apoptosis and Sow Fertility

Wang,

Sheng,

Zhang

et al. 2024

Advanced Science

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Sow fertility is an economically important quantitative trait. Hundreds of quantitative trait loci (QTLs) containing tens of thousands of potential candidate genes are excavated. However, among these genes, non‐coding RNAs including long non‐coding RNAs (lncRNAs) are often overlooked. Here, it is reported that NORSF is a novel causal lncRNA for sow fertility traits in QTLs. QTLs are characterized for sow fertility traits at the genome‐wide level and identified 4,630 potential candidate lncRNAs, with 13 differentially expressed during sow follicular atresia. NORSF, a lncRNA that involved in sow granulosa cell (sGC) function, is identified as a candidate gene for sow fertility traits as a G to A transversion at 128 nt in its transcript is shown to be markedly associated with sow fertility traits. Mechanistically, after forming the RNA:dsDNA triplexes with the promoter of Caspase8, NORSF transcript with allele G binds to an RNA‐binding protein (RBP) NR2C1 and recruits it to the promoter of Caspase8, to induce Caspase8 transcription in sGCs. Functionally, this leads to a loss of inducing effect of NORSF on sGC apoptosis by inactivating the death receptor‐mediated apoptotic pathway. This study identified a novel causal lncRNA that can be used for the genetic improvement of sow fertility traits.

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Lnc2300 is a cis‐acting long noncoding RNA of CYP11A1 in ovarian granulosa cells

Wang

et al. 2022

Journal Cellular Physiology

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The high level of progesterone and 17β-estradiol ratio (P4/E2) in follicular fluid has been considered as a biomarker of follicular atresia. CYP11A1, the crucial gene encoding the rate-limiting enzyme for steroid hormone synthesis, has been reported differently expressed in the ovary during follicular atresia. However, the regulation mechanism of CYP11A1 expression during follicular atresia still remains unclear.Here, we have demonstrated that lnc2300, a novel pig ovary-specific highly expressed cis-acting long noncoding RNA (lncRNA) transcribed from chromosome 7, has the ability to induce the expression of CYP11A1 and inhibit the apoptosis of porcine granulosa cells (GCs). Mechanistically, lnc2300, mainly located in the cytoplasm of porcine GCs, sponges and suppresses the expression of miR-365-3p through acting as a competing endogenous RNA (ceRNA), which further relieves the inhibitory effects of miR-365-3p on the expression of CYP11A1. Besides, CYP11A1 is validated as a direct functional target of miR-365-3p in porcine GCs. Functionally, lnc2300 is an antiapoptotic lncRNA that reduces porcine GC apoptosis by inhibiting the proapoptotic function of miR-365-3p. In summary, our findings reveal a cisacting regulation mechanism of CYP11A1 through lncRNA, and define a novel signaling pathway, lnc2300/miR-365-3p/CYP11A1 axis, which is involved in the regulation of GC apoptosis and follicular atresia.

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NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis

Cited by 23 publications

References 66 publications

A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress

A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress

A Mutation Losing an RBP‐Binding Site in the LncRNA NORSF Transcript Influences Granulosa Cell Apoptosis and Sow Fertility

Lnc2300 is a cis‐acting long noncoding RNA of CYP11A1 in ovarian granulosa cells

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