Jiayu Chen, Zhuolin Zhou, Yang Shen, Xinyao Hu, Yukai Chen, Le Xu, Ling Wang, Junhua Li, Ximing Xu
{"title":"m6a修饰的circCCAR1通过增强KIF5B在肝细胞癌中的表达促进恶性增殖。","authors":"Jiayu Chen, Zhuolin Zhou, Yang Shen, Xinyao Hu, Yukai Chen, Le Xu, Ling Wang, Junhua Li, Ximing Xu","doi":"10.1007/s13105-025-01112-8","DOIUrl":null,"url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is known for its aggressive nature and high mortality rates. Circular RNAs (circRNAs) have emerged as critical regulators of cancer progression, yet the role of the circRNA cell division cycle and apoptosis regulator 1 (circCCAR1) in HCC is poorly understood. This study aims to explore the mechanism of circCCAR1 in HCC progression. We measured the expression of circCCAR1, miR-641, and motor protein kinesin family member 5B (KIF5B) in HCC cell lines and normal hepatic cells, revealing that circCCAR1 was significantly overexpressed in HCC. Mechanistic analyses showed that the RNA methyltransferase YTH domain-containing protein 1 (YTHDC1) recognized N6-methyladenosine (m6A) modifications on circCCAR1, facilitating its transport from the nucleus to the cytoplasm. In the cytoplasm, circCCAR1 acted as a molecular sponge to sequester miR-641, relieving miR-641-mediated inhibition of KIF5B mRNA. CircCCAR1 directly bound to the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), which stabilized KIF5B mRNA. Functional experiments demonstrated that silencing circCCAR1 suppressed HCC cell proliferation, induced apoptosis, and reduced tumor growth in a xenograft mouse model, effects that were partially reversed after KIF5B overexpression or miR-641 inhibition. In conclusion, YTHDC1 promotes the cytoplasmic translocation of m6A-modified circCCAR1 and circCCAR1 facilitates HCC progression through the miR-641/KIF5B axis.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"815-829"},"PeriodicalIF":4.3000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"m6A-modified circCCAR1 promotes malignant proliferation by enhancing KIF5B expression in hepatocellular carcinoma.\",\"authors\":\"Jiayu Chen, Zhuolin Zhou, Yang Shen, Xinyao Hu, Yukai Chen, Le Xu, Ling Wang, Junhua Li, Ximing Xu\",\"doi\":\"10.1007/s13105-025-01112-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Hepatocellular carcinoma (HCC) is known for its aggressive nature and high mortality rates. Circular RNAs (circRNAs) have emerged as critical regulators of cancer progression, yet the role of the circRNA cell division cycle and apoptosis regulator 1 (circCCAR1) in HCC is poorly understood. This study aims to explore the mechanism of circCCAR1 in HCC progression. We measured the expression of circCCAR1, miR-641, and motor protein kinesin family member 5B (KIF5B) in HCC cell lines and normal hepatic cells, revealing that circCCAR1 was significantly overexpressed in HCC. Mechanistic analyses showed that the RNA methyltransferase YTH domain-containing protein 1 (YTHDC1) recognized N6-methyladenosine (m6A) modifications on circCCAR1, facilitating its transport from the nucleus to the cytoplasm. In the cytoplasm, circCCAR1 acted as a molecular sponge to sequester miR-641, relieving miR-641-mediated inhibition of KIF5B mRNA. CircCCAR1 directly bound to the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), which stabilized KIF5B mRNA. Functional experiments demonstrated that silencing circCCAR1 suppressed HCC cell proliferation, induced apoptosis, and reduced tumor growth in a xenograft mouse model, effects that were partially reversed after KIF5B overexpression or miR-641 inhibition. In conclusion, YTHDC1 promotes the cytoplasmic translocation of m6A-modified circCCAR1 and circCCAR1 facilitates HCC progression through the miR-641/KIF5B axis.</p>\",\"PeriodicalId\":16779,\"journal\":{\"name\":\"Journal of physiology and biochemistry\",\"volume\":\" \",\"pages\":\"815-829\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of physiology and biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s13105-025-01112-8\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of physiology and biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13105-025-01112-8","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
m6A-modified circCCAR1 promotes malignant proliferation by enhancing KIF5B expression in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is known for its aggressive nature and high mortality rates. Circular RNAs (circRNAs) have emerged as critical regulators of cancer progression, yet the role of the circRNA cell division cycle and apoptosis regulator 1 (circCCAR1) in HCC is poorly understood. This study aims to explore the mechanism of circCCAR1 in HCC progression. We measured the expression of circCCAR1, miR-641, and motor protein kinesin family member 5B (KIF5B) in HCC cell lines and normal hepatic cells, revealing that circCCAR1 was significantly overexpressed in HCC. Mechanistic analyses showed that the RNA methyltransferase YTH domain-containing protein 1 (YTHDC1) recognized N6-methyladenosine (m6A) modifications on circCCAR1, facilitating its transport from the nucleus to the cytoplasm. In the cytoplasm, circCCAR1 acted as a molecular sponge to sequester miR-641, relieving miR-641-mediated inhibition of KIF5B mRNA. CircCCAR1 directly bound to the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), which stabilized KIF5B mRNA. Functional experiments demonstrated that silencing circCCAR1 suppressed HCC cell proliferation, induced apoptosis, and reduced tumor growth in a xenograft mouse model, effects that were partially reversed after KIF5B overexpression or miR-641 inhibition. In conclusion, YTHDC1 promotes the cytoplasmic translocation of m6A-modified circCCAR1 and circCCAR1 facilitates HCC progression through the miR-641/KIF5B axis.
期刊介绍:
The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.