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DIRAS1 knockdown enhances proliferation, growth, migration, and invasion of C33A and SiHa cells, while DIRAS1 overexpression reduces viability and motility. DIRAS1 mRNA and protein levels are decreased in tumor versus para-cancer tissues and negatively correlate with pathological grades. Epigenetic modulators and m6A regulators show that m6A pathways may control DIRAS1 mRNA stability and translation efficiency.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/m6a-modification-regulates-tumor-suppressor-diras1-expression-in-cervical-cancer-cells/326975/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/m6a-modification-regulates-tumor-suppressor-diras1-expression-in-cervical-cancer-cells/326975.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of the study?","Question",{"text":112,"@type":113},"The study examines how m6A modification affects DIRAS1 expression and whether DIRAS1 functions as a tumor suppressor in cervical cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do changes in DIRAS1 affect cervical cancer cell behavior?",{"text":117,"@type":113},"DIRAS1 knockdown significantly promotes proliferation, growth, migration, and invasion, while DIRAS1 overexpression inhibits viability and motility.",{"name":119,"@type":110,"acceptedAnswer":120},"Which epigenetic regulators are linked to DIRAS1 expression in this work?",{"text":121,"@type":113},"DNA methylation inhibitor 5-Azacytidine and histone deacetylation inhibitor SAHA increase DIRAS1 mRNA, while the FTO inhibitor FB23–2 decreases DIRAS1 mRNA but increases DIRAS1 protein; METTL3/METTL14 and FTO/ALKBH5 perturbations also modulate DIRAS1 protein levels.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},326975,1790901559,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","CANCER BIOLOGY & THERAPY  \n2024, VOL. 25, NO. 1, 2306674 [https://doi.org/10.1080/15384047.2024.2306674](https://doi.org/10.1080/15384047.2024.2306674)  \nRESEARCH PAPER     \nM6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells  \nYu-Yan Wanga\\#, Lian-Hua Yeb\\#, An-Qi Zhaoc, Wei-Ran Gaod, Ning Daid, Yu Yine, and Xin Zhang d  \naDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China; bDepartment of Internal Medicine, Zigong Fourth People’s Hospital, Zigong, Sichuan, China; cDepartment of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University, Beijing, China; dDepartment of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China; eOperating Rooms, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China  \nABSTRACT  \nDIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in vitro. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23–2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant antioncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.  \nARTICLE HISTORY  \nReceived 22 October 2023 Revised 2 January 2024 Accepted 14 January 2024  \nKEYWORDS  \nCervical cancer; DIRAS1; epigenetic regulation; m6A  \nIntroduction  \nCervical cancer is considered almost entirely preventable because of highly effective primary (HPV vaccine) and secondary (screening) prevention measures. 1 In 2018, the Director-General of the World Health Organization (WHO) called for global action to eliminate cervical cancer (≤4 per 100,000 women globally) through a triple-intervention strategy, that is projected to be achieved in the next century.2,3 However, until this goal is achieved, there will still be many women with advanced cervical cancer who have limited treatment options.4 Exploring potential targeted therapies holds promise for the treatment of persistent, recurrent and metastatic cervical cancer.4  \nDIRAS family GTPase 1 (DIRAS1), also known as Rig (Rasrelated inhibitor of cell growth), is a member of the small GTPase Ras superfamily.5 The DIRAS1 gene, located on chromosome 19p13.3, consists of 2 exons and encodes a protein of 198 amino acids. Unlike common oncogenic small GTPases (e.g., Ras or Rho family members), DIRAS1 has been reported as a potential tumor suppressor in human renal cell carcinoma,6 ovarian cancer,7 colorectal cancer,8 gliomas,9 and esophageal squamous cell carcinoma. 10 However, its  \nexpression pattern and role in cervical cancer remain unknown.  \nEpigenetic","cbCaigl9ikt96iQJ","https://ap.wps.com/l/cbCaigl9ikt96iQJ","pdf",5452133,"English","# Introduction\n## DIRAS1 in cervical cancer\n## Epigenetic regulation and m6A mechanisms\n# Abstract Findings","[{\"question\":\"What is the main focus of the study?\",\"answer\":\"The study examines how m6A modification affects DIRAS1 expression and whether DIRAS1 functions as a tumor suppressor in cervical cancer cells.\"},{\"question\":\"How do changes in DIRAS1 affect cervical cancer cell behavior?\",\"answer\":\"DIRAS1 knockdown significantly promotes proliferation, growth, migration, and invasion, while DIRAS1 overexpression inhibits viability and motility.\"},{\"question\":\"Which epigenetic regulators are linked to DIRAS1 expression in this work?\",\"answer\":\"DNA methylation inhibitor 5-Azacytidine and histone deacetylation inhibitor SAHA increase DIRAS1 mRNA, while the FTO inhibitor FB23–2 decreases DIRAS1 mRNA but increases DIRAS1 protein; METTL3/METTL14 and FTO/ALKBH5 perturbations also modulate DIRAS1 protein levels.\"}]","M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells | PDF",1789975895,23]