N4-Acetylcytidine Of Circxpo6 Triggers Mapk Pathway To Promote Pulpitis
Although N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether it exists in circular non-coding RNAs (circRNA), and the molecular mechanism on circRNA remains elusive. We performed circRNA microarray assay to reveal the...
Gespeichert in:
| Veröffentlicht in: | International dental journal Jg. 75; S. 104789 |
|---|---|
| 1. Verfasser: | |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
Elsevier Inc
01.10.2025
Elsevier |
| Schlagworte: | |
| ISSN: | 0020-6539 |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Although N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether it exists in circular non-coding RNAs (circRNA), and the molecular mechanism on circRNA remains elusive.
We performed circRNA microarray assay to reveal the expression patterns of circRNA involved in pulpitis. circXPO6 was identified and verified as a critical factor by qRT-PCR in pulpitis. The gain- and loss-of-function studies were performed to investigate the biological role of circXPO6 in regulating pulpitis progression. By combining the analyses of ac4C-RIP (acRIP) and NAT10-RIP, we found a critical ac4C modification of circXPO6. In addition, through nuclear cytoplasmic separation, acRIP, and acetylation mutant construct experiments, the impact of circRNA acetylation levels on circRNA self-function was analyzed to explore its potentiality in the progression of pulpitis.
Herein, we identified ac4C modified circRNA, circXPO6, upregulated in pulpitis tissues, and promoted the inflammatory response in pulpitis. We further reveal that NAT10 contributed to the ac4C modifications of circXPO6 in pulpitis, indicating that the expression of circXPO6 was regulated by NAT10 in an ac4C-acetylation-dependent manner. Importantly, the inhibited ac4C modification of circXPO6 increases export to the cytoplasm in pulpitis, further activating the p38MAPK cascade pathway, ultimately accelerating the progression of pulpitis.
Consequently, this study highlights that the ac4C modification of circXPO6 modulates cytoplasmic export and triggers p38MAPK pathway to promote inflammatory response in pulpitis and proposes a promising strategy to alleviate the development of pulpitis. |
|---|---|
| AbstractList | Aim or purpose: Although N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether it exists in circular non-coding RNAs (circRNA), and the molecular mechanism on circRNA remains elusive. Materials and methods: We performed circRNA microarray assay to reveal the expression patterns of circRNA involved in pulpitis. circXPO6 was identified and verified as a critical factor by qRT-PCR in pulpitis. The gain- and loss-of-function studies were performed to investigate the biological role of circXPO6 in regulating pulpitis progression. By combining the analyses of ac4C-RIP (acRIP) and NAT10-RIP, we found a critical ac4C modification of circXPO6. In addition, through nuclear cytoplasmic separation, acRIP, and acetylation mutant construct experiments, the impact of circRNA acetylation levels on circRNA self-function was analyzed to explore its potentiality in the progression of pulpitis. Results: Herein, we identified ac4C modified circRNA, circXPO6, upregulated in pulpitis tissues, and promoted the inflammatory response in pulpitis. We further reveal that NAT10 contributed to the ac4C modifications of circXPO6 in pulpitis, indicating that the expression of circXPO6 was regulated by NAT10 in an ac4C-acetylation-dependent manner. Importantly, the inhibited ac4C modification of circXPO6 increases export to the cytoplasm in pulpitis, further activating the p38MAPK cascade pathway, ultimately accelerating the progression of pulpitis. Conclusions: Consequently, this study highlights that the ac4C modification of circXPO6 modulates cytoplasmic export and triggers p38MAPK pathway to promote inflammatory response in pulpitis and proposes a promising strategy to alleviate the development of pulpitis. Although N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether it exists in circular non-coding RNAs (circRNA), and the molecular mechanism on circRNA remains elusive. We performed circRNA microarray assay to reveal the expression patterns of circRNA involved in pulpitis. circXPO6 was identified and verified as a critical factor by qRT-PCR in pulpitis. The gain- and loss-of-function studies were performed to investigate the biological role of circXPO6 in regulating pulpitis progression. By combining the analyses of ac4C-RIP (acRIP) and NAT10-RIP, we found a critical ac4C modification of circXPO6. In addition, through nuclear cytoplasmic separation, acRIP, and acetylation mutant construct experiments, the impact of circRNA acetylation levels on circRNA self-function was analyzed to explore its potentiality in the progression of pulpitis. Herein, we identified ac4C modified circRNA, circXPO6, upregulated in pulpitis tissues, and promoted the inflammatory response in pulpitis. We further reveal that NAT10 contributed to the ac4C modifications of circXPO6 in pulpitis, indicating that the expression of circXPO6 was regulated by NAT10 in an ac4C-acetylation-dependent manner. Importantly, the inhibited ac4C modification of circXPO6 increases export to the cytoplasm in pulpitis, further activating the p38MAPK cascade pathway, ultimately accelerating the progression of pulpitis. Consequently, this study highlights that the ac4C modification of circXPO6 modulates cytoplasmic export and triggers p38MAPK pathway to promote inflammatory response in pulpitis and proposes a promising strategy to alleviate the development of pulpitis. Aim or purposeAlthough N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether it exists in circular non-coding RNAs (circRNA), and the molecular mechanism on circRNA remains elusive. Materials and methodsWe performed circRNA microarray assay to reveal the expression patterns of circRNA involved in pulpitis. circXPO6 was identified and verified as a critical factor by qRT-PCR in pulpitis. The gain- and loss-of-function studies were performed to investigate the biological role of circXPO6 in regulating pulpitis progression. By combining the analyses of ac4C-RIP (acRIP) and NAT10-RIP, we found a critical ac4C modification of circXPO6. In addition, through nuclear cytoplasmic separation, acRIP, and acetylation mutant construct experiments, the impact of circRNA acetylation levels on circRNA self-function was analyzed to explore its potentiality in the progression of pulpitis. ResultsHerein, we identified ac4C modified circRNA, circXPO6, upregulated in pulpitis tissues, and promoted the inflammatory response in pulpitis. We further reveal that NAT10 contributed to the ac4C modifications of circXPO6 in pulpitis, indicating that the expression of circXPO6 was regulated by NAT10 in an ac4C-acetylation-dependent manner. Importantly, the inhibited ac4C modification of circXPO6 increases export to the cytoplasm in pulpitis, further activating the p38MAPK cascade pathway, ultimately accelerating the progression of pulpitis. ConclusionsConsequently, this study highlights that the ac4C modification of circXPO6 modulates cytoplasmic export and triggers p38MAPK pathway to promote inflammatory response in pulpitis and proposes a promising strategy to alleviate the development of pulpitis. |
| ArticleNumber | 104789 |
| Author | Lin, Li |
| Author_xml | – sequence: 1 givenname: Li surname: Lin fullname: Lin, Li organization: Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China |
| BookMark | eNqVkdtq3EAMhn2RQnPoG-TCL-Ct5mgbSiEsbRpIk4VsroexrNmO43iWGaet3752XXpXSq4EAn2Svv8sOxnCQFl2yWDDgOn33ca3NIzdhgNXc0uWVX2SnQJwKLQS9dvsLKUOQFYC9Gl2fSeLK6Rx6nEafesHyu9dvvURfx6DzvfRHw4UU_7VHp_ynR2__bBTvg_5LobnMFK-e-mPfvTpInvjbJ_o3Z96nj1-_rTffilu769vtle3BQoOdcFbVfGy0RwQhcCy1Vw4qSW1FWlVNcRI1YwqZHVDDiyWTqGoQAmlUUkuzrObldsG25lj9M82TiZYb343QjwYG0ePPRntZNvK0iGvmAQla-GgkaqsGsBSgptZcmVhDClFcn95DMwi03RmlWkWmWaVOY99XMdo_vO7p2gSehqQWh8Jx_kQ_1oA9n7waPsnmih14SUOs0PDTOIGzMOS3RIdVyCh5Avgw78B_9__C8DtqnA |
| ContentType | Journal Article |
| Copyright | 2025 |
| Copyright_xml | – notice: 2025 |
| DBID | 6I. AAFTH AAYXX CITATION DOA |
| DOI | 10.1016/j.identj.2025.104789 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef |
| DatabaseTitleList | |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Dentistry |
| EndPage | 104789 |
| ExternalDocumentID | oai_doaj_org_article_6f4dd47fc281405493f0b4578b0c740f 10_1016_j_identj_2025_104789 S0020653925040729 1_s2_0_S0020653925040729 |
| GroupedDBID | --- .1- .FO .GA .Y3 05W 0R~ 1OC 31~ 3SF 50Z 52M 52U 52V 53G 5GY 8-0 8-1 8-3 8-4 8-5 930 A03 AAEDW AAESR AAEVG AALRI AAMMB AANHP AAONW AAWTL AAXUO AAYWO AAZKR ABCUV ABLJU ABPVW ACBWZ ACGFO ACGFS ACMXC ACPOU ACPRK ACRPL ACVFH ACXQS ACYXJ ADBBV ADCNI ADEOM ADIZJ ADKYN ADMGS ADNMO ADVLN ADXAS ADZMN AEFGJ AEIMD AENEX AEUPX AFBPY AFFNX AFGKR AFJKZ AFPUW AFRHN AGQPQ AGXDD AHMBA AIDQK AIDYY AIGII AITUG AIURR AJAOE AJUYK AKBMS AKRWK AKYEP ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMRAJ AMYDB APXCP ASPBG ATUGU AVWKF AZBYB AZFZN AZVAB BAFTC BDRZF BHBCM BMXJE BRXPI CS3 D-E D-F DCZOG DPXWK DRFUL DRMAN DRSTM EBS EJD F00 F01 F04 F5P FDB FEDTE FUBAC G-S GK1 GODZA GROUPED_DOAJ H.T H.X HF~ HVGLF HZ~ LH4 LITHE LOXES LUTES LW6 LYRES MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM MY~ N04 N05 NF~ O66 O8X O9- OK1 P2P P2W P2X PQQKQ Q.N QB0 R.K ROL RPM SUPJJ UB1 V8K W8V WBKPD WBNRW WIH WIJ WIK WOHZO WPGGZ XG2 Z5R ZGI ZZTAW ~WT 6I. AAFTH AAYXX CITATION |
| ID | FETCH-LOGICAL-c3209-2d5827b620cc33c7d623f464ed8e658be1e591e8c19bef0ac7f5c3805356c5423 |
| IEDL.DBID | DOA |
| ISSN | 0020-6539 |
| IngestDate | Mon Nov 10 19:21:30 EST 2025 Sat Nov 29 06:57:59 EST 2025 Sat Nov 29 17:01:37 EST 2025 Sat Nov 29 12:11:03 EST 2025 Sat Nov 29 06:57:23 EST 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | Pulpitis circXPO6 N4-acetylcytidine modification |
| Language | English |
| License | http://creativecommons.org/licenses/by-nc-nd/4.0 |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c3209-2d5827b620cc33c7d623f464ed8e658be1e591e8c19bef0ac7f5c3805356c5423 |
| OpenAccessLink | https://doaj.org/article/6f4dd47fc281405493f0b4578b0c740f |
| PageCount | 1 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_6f4dd47fc281405493f0b4578b0c740f crossref_primary_10_1016_j_identj_2025_104789 elsevier_sciencedirect_doi_10_1016_j_identj_2025_104789 elsevier_clinicalkeyesjournals_1_s2_0_S0020653925040729 elsevier_clinicalkey_doi_10_1016_j_identj_2025_104789 |
| PublicationCentury | 2000 |
| PublicationDate | October 2025 |
| PublicationDateYYYYMMDD | 2025-10-01 |
| PublicationDate_xml | – month: 10 year: 2025 text: October 2025 |
| PublicationDecade | 2020 |
| PublicationTitle | International dental journal |
| PublicationYear | 2025 |
| Publisher | Elsevier Inc Elsevier |
| Publisher_xml | – name: Elsevier Inc – name: Elsevier |
| SSID | ssj0048306 |
| Score | 2.4054444 |
| Snippet | Although N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether it exists in... Aim or purposeAlthough N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether... Aim or purpose: Although N4-acetylcytidine (ac4C) modification affects the stability of mRNA, and lncRNA, and regulates miRNA production, it is unknown whether... |
| SourceID | doaj crossref elsevier |
| SourceType | Open Website Index Database Publisher |
| StartPage | 104789 |
| SubjectTerms | circXPO6 Dentistry N4-acetylcytidine modification Pulpitis |
| Title | N4-Acetylcytidine Of Circxpo6 Triggers Mapk Pathway To Promote Pulpitis |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S0020653925040729 https://www.clinicalkey.es/playcontent/1-s2.0-S0020653925040729 https://dx.doi.org/10.1016/j.identj.2025.104789 https://doaj.org/article/6f4dd47fc281405493f0b4578b0c740f |
| Volume | 75 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals issn: 0020-6539 databaseCode: DOA dateStart: 20210101 customDbUrl: isFulltext: true dateEnd: 99991231 titleUrlDefault: https://www.doaj.org/ omitProxy: false ssIdentifier: ssj0048306 providerName: Directory of Open Access Journals – providerCode: PRVWIB databaseName: Wiley Online Library Full Collection 2020 issn: 0020-6539 databaseCode: DRFUL dateStart: 19970101 customDbUrl: isFulltext: true dateEnd: 99991231 titleUrlDefault: https://onlinelibrary.wiley.com omitProxy: false ssIdentifier: ssj0048306 providerName: Wiley-Blackwell |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LTxsxELYQVKIXBG1RQwvygevSXT_2cQRC6CGECIWKm5Ud2yhplURJoOTfd8a7i4KElEuvq7W9O37M92nG3zB2mnkrIZYuEl7KSPlERTlIH6XWaWRBiDFC9PxXN-v18oeHor9W6otywip54MpwP1KvrFWZB0HaTMhmpI9LheusjCFTsafTF1FPQ6aqM1jlMlTVjAM50rJoLs2FzC6q1rkcIzcU-iyo0xRvnFLQ7l_zTWv-prPP9mqgyM-rDzxgW27yie22KbmH6rN9Ztc9FZ2DW67-wGo5Qhfk-K3nl6M5vMymKR8g7X5EbMdvhrPfvI9A7-9wxQdT3g8JeI73Q93h0eILu-9cDS5_RnVZhAikoHiI1bnIylTEAFJCZhHBeJUqZ3OHeKJ0idNF4nJIitL5eAiZ1yBzEnJJQSN8OmTbk-nEfWVcIhtS4LXW3iuwqhCitDYRpUw9hXBbLGrsYmaV-oVp0sLGprKjITuayo4tdkHGe32XtKvDA5xRU8-o2TSjLaYb05vmeigeaNjRaMPg2Xvt3KLelQuTmIUwsaEAdZDkJfk2Uk5fb1kDjwpQbBzz6H_88Df2kbokjyjS72x7OX9yx-wDPOMamJ-EhX3Cdtp3nfvuP35U-ek |
| linkProvider | Directory of Open Access Journals |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=N4-Acetylcytidine+Of+Circxpo6+Triggers+Mapk+Pathway+To+Promote+Pulpitis&rft.jtitle=International+dental+journal&rft.au=Lin%2C+Li&rft.date=2025-10-01&rft.pub=Elsevier+Inc&rft.issn=0020-6539&rft.volume=75&rft_id=info:doi/10.1016%2Fj.identj.2025.104789&rft.externalDocID=S0020653925040729 |
| thumbnail_m | http://cvtisr.summon.serialssolutions.com/2.0.0/image/custom?url=https%3A%2F%2Fcdn.clinicalkey.com%2Fck-thumbnails%2F00206539%2FS0020653925X00071%2Fcov150h.gif |