Meihua Shan , Dong Liu , Liangbo Sun , Mingzhen Yang , Meng He , Yang Zhang , Li Xiang , Lu Lu , Haiyan He , Dun Niu , Lingxi Chen , Shuhui Li , An Chen , Fengtian He , Yue Wang , Jiqin Lian
{"title":"KIAA1429 通过 m6A-YTHDC1 依赖性 RND3 下调促进肝癌细胞转移","authors":"Meihua Shan , Dong Liu , Liangbo Sun , Mingzhen Yang , Meng He , Yang Zhang , Li Xiang , Lu Lu , Haiyan He , Dun Niu , Lingxi Chen , Shuhui Li , An Chen , Fengtian He , Yue Wang , Jiqin Lian","doi":"10.1016/j.canlet.2023.216598","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>N6-methyladenosine (m6A), a dynamically reversible modification in eukaryotic RNAs<span>, modulates gene expression and pathological processes in various tumors. KIAA1429, the largest component of the m6A </span></span>methyltransferase<span><span><span> complex, plays an important role in m6A modification. However, the underlying mechanism of KIAA1429 in hepatocellular carcinoma (HCC) remains largely unknown. Immunohistochemical assay was performed to examine the expression of KIAA1429 in HCC tissues. Transwell, wound healing and animal experiments were used to investigate the influence of KIAA1429 on cell migration and invasion. The mRNA high‐throughput sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed to screen the downstream target of KIAA1429. </span>RNA stability assays, RNA immunoprecipitation assay (RIP), MeRIP-qPCR and </span>luciferase<span> assay were used to evaluate the relationship between KIAA1429 and the m6A-modified genes. Results showed that the expression level of KIAA1429 was significantly higher in HCC tissues than in adjacent tissues, and the upregulation of KIAA1429 could promote HCC metastasis </span></span></span><em>in vitro</em> and <em>in vivo</em><span><span>. Mechanistically, we confirmed that KIAA1429 negatively regulated the tumor suppressor, Rho family </span>GTPase<span> 3 (RND3), by decreasing its mRNA stability<span> in coordination with the m6A reader YTHDC1. Moreover, we demonstrated that KIAA1429 could regulate the m6A modification of RND3 mRNA via its RNA binding domain. Our data indicated that KIAA1429 exerted its oncogenic role by inhibiting RND3 expression in an m6A-dependent manner, suggesting that KIAA1429 might be a potential prognostic biomarker and therapeutic target in HCC.</span></span></span></p></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"584 ","pages":"Article 216598"},"PeriodicalIF":10.1000,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells\",\"authors\":\"Meihua Shan , Dong Liu , Liangbo Sun , Mingzhen Yang , Meng He , Yang Zhang , Li Xiang , Lu Lu , Haiyan He , Dun Niu , Lingxi Chen , Shuhui Li , An Chen , Fengtian He , Yue Wang , Jiqin Lian\",\"doi\":\"10.1016/j.canlet.2023.216598\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>N6-methyladenosine (m6A), a dynamically reversible modification in eukaryotic RNAs<span>, modulates gene expression and pathological processes in various tumors. KIAA1429, the largest component of the m6A </span></span>methyltransferase<span><span><span> complex, plays an important role in m6A modification. However, the underlying mechanism of KIAA1429 in hepatocellular carcinoma (HCC) remains largely unknown. Immunohistochemical assay was performed to examine the expression of KIAA1429 in HCC tissues. Transwell, wound healing and animal experiments were used to investigate the influence of KIAA1429 on cell migration and invasion. The mRNA high‐throughput sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed to screen the downstream target of KIAA1429. </span>RNA stability assays, RNA immunoprecipitation assay (RIP), MeRIP-qPCR and </span>luciferase<span> assay were used to evaluate the relationship between KIAA1429 and the m6A-modified genes. Results showed that the expression level of KIAA1429 was significantly higher in HCC tissues than in adjacent tissues, and the upregulation of KIAA1429 could promote HCC metastasis </span></span></span><em>in vitro</em> and <em>in vivo</em><span><span>. Mechanistically, we confirmed that KIAA1429 negatively regulated the tumor suppressor, Rho family </span>GTPase<span> 3 (RND3), by decreasing its mRNA stability<span> in coordination with the m6A reader YTHDC1. Moreover, we demonstrated that KIAA1429 could regulate the m6A modification of RND3 mRNA via its RNA binding domain. Our data indicated that KIAA1429 exerted its oncogenic role by inhibiting RND3 expression in an m6A-dependent manner, suggesting that KIAA1429 might be a potential prognostic biomarker and therapeutic target in HCC.</span></span></span></p></div>\",\"PeriodicalId\":9506,\"journal\":{\"name\":\"Cancer letters\",\"volume\":\"584 \",\"pages\":\"Article 216598\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2024-01-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0304383523005499\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304383523005499","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells
N6-methyladenosine (m6A), a dynamically reversible modification in eukaryotic RNAs, modulates gene expression and pathological processes in various tumors. KIAA1429, the largest component of the m6A methyltransferase complex, plays an important role in m6A modification. However, the underlying mechanism of KIAA1429 in hepatocellular carcinoma (HCC) remains largely unknown. Immunohistochemical assay was performed to examine the expression of KIAA1429 in HCC tissues. Transwell, wound healing and animal experiments were used to investigate the influence of KIAA1429 on cell migration and invasion. The mRNA high‐throughput sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed to screen the downstream target of KIAA1429. RNA stability assays, RNA immunoprecipitation assay (RIP), MeRIP-qPCR and luciferase assay were used to evaluate the relationship between KIAA1429 and the m6A-modified genes. Results showed that the expression level of KIAA1429 was significantly higher in HCC tissues than in adjacent tissues, and the upregulation of KIAA1429 could promote HCC metastasis in vitro and in vivo. Mechanistically, we confirmed that KIAA1429 negatively regulated the tumor suppressor, Rho family GTPase 3 (RND3), by decreasing its mRNA stability in coordination with the m6A reader YTHDC1. Moreover, we demonstrated that KIAA1429 could regulate the m6A modification of RND3 mRNA via its RNA binding domain. Our data indicated that KIAA1429 exerted its oncogenic role by inhibiting RND3 expression in an m6A-dependent manner, suggesting that KIAA1429 might be a potential prognostic biomarker and therapeutic target in HCC.
期刊介绍:
Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research.
Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy.
By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.