Dataset Information

N⁶ -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating β-catenin ubiquitination and degradation.

ABSTRACT:

Objectives

N⁶ -methyladenosine (m6A) is one of the most abundant internal RNA modifications. We investigated the role of m6A-modified circRERE in osteoarthritis (OA) and its mechanism.

Materials and methods

CircRERE and IRF2BPL were screened by microarrays. The role of m6A-modification in circRERE was examined by methylated RNA precipitation and morpholino oligo (MOs) treatment. The axis of circRERE/miR-195-5p/IRF2BPL/β-catenin was determined using flow cytometry, western blotting and immunofluorescence in human chondrocytes (HCs) and corroborated using a mouse model of destabilization of medial meniscus (DMM) with intra-articular (IA) injection of adeno-associated viruses (AAV).

Results

CircRERE was decreased in OA cartilage and chondrocytes compared with control. CircRERE downregulation was likely attributed to its increased m6A modification prone to endoribonucleolytic cleavage by YTHDF2-HRSP12-RNase P/MRP in OA chondrocytes. MOs transfection targeting HRSP12 binding motifs in circRERE partially reversed decreased circRERE expression and increased apoptosis in HCs treated with IL-1β for 6 h. CircRERE exerted chondroprotective effects by targeting miR-195-5p/IRF2BPL, thus regulating the ubiquitination and degradation of β-catenin. CircRere (mouse homologue) overexpression by IA-injection of AAV-circRere into mice attenuated the severity of DMM-induced OA, whereas AAV-miR-195a-5p or AAV-sh-Irf2bpl reduced the protective effects. The detrimental effects of AAV-sh-Irf2bpl on DMM-induced OA were substantially counteracted by ICG-001, an inhibitor of β-catenin.

Conclusions

Our study is a proof-of-concept demonstration for targeting m6A-modified circRERE and its target miR-195-5p/IRF2BPL/β-catenin as potential therapeutic strategies for OA treatment.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9816929 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

N<sup>6</sup> -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating β-catenin ubiquitination and degradation.

Liu Yuxi Y Yang Yunhan Y Lin Yucheng Y Wei Bing B Hu Xinyue X Xu Li L Zhang Weituo W Lu Jun J

Cell proliferation 20220622 1

<h4>Objectives</h4>N<sup>6</sup> -methyladenosine (m6A) is one of the most abundant internal RNA modifications. We investigated the role of m6A-modified circRERE in osteoarthritis (OA) and its mechanism.<h4>Materials and methods</h4>CircRERE and IRF2BPL were screened by microarrays. The role of m6A-modification in circRERE was examined by methylated RNA precipitation and morpholino oligo (MOs) treatment. The axis of circRERE/miR-195-5p/IRF2BPL/β-catenin was determined using flow cytometry, weste ...[more]

PMID: 35733354

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Dataset Information

N⁶ -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating β-catenin ubiquitination and degradation.

Objectives

Materials and methods

Results

Conclusions

Publications

N<sup>6</sup> -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating β-catenin ubiquitination and degradation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

N6 -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating β-catenin ubiquitination and degradation.

Objectives

Materials and methods

Results

Conclusions

Publications

N<sup>6</sup> -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating β-catenin ubiquitination and degradation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

N⁶ -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating β-catenin ubiquitination and degradation.