hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p
Abstract Circular RNAs (circRNAs) are widely involved in diverse biological processes of cancers. Nonetheless, the potential function of hsa_circ_0008305 in hepatocellular carcinoma (HCC) remains largely unknown. This study aims to elucidate the role and underlying mechanism of hsa_circ_0008305 in H...
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Nature Portfolio
2025-01-01
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| author | Shenglan Huang Kan Liu Yongkan Xu Hua Wang Shumin Fu Jianbing Wu |
| author_facet | Shenglan Huang Kan Liu Yongkan Xu Hua Wang Shumin Fu Jianbing Wu |
| author_sort | Shenglan Huang |
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| description | Abstract Circular RNAs (circRNAs) are widely involved in diverse biological processes of cancers. Nonetheless, the potential function of hsa_circ_0008305 in hepatocellular carcinoma (HCC) remains largely unknown. This study aims to elucidate the role and underlying mechanism of hsa_circ_0008305 in HCC. Our findings reveal that the novel circRNA hsa_circ_0008305 (circPTK2) is significantly upregulated in HCC tissues, with its elevated expression being positively correlated with advanced tumor T stage and vascular invasion. The circular characteristics and subcellular localization of hsa_circ_0008305 was determined by RNase R treatment and RNA nucleocytoplasmic separation. Further functional assays, including CCK8, EdU, colony formation assays, scratch-healing, transwell assays, and Xenograft tumor models were conducted to explore the biological functions of circPTK2. The regulatory mechanisms of circPTK2 were elucidated through RNA sequencing, enrichment analysis, and dual luciferase reporter assay. Our findings indicate that circPTK2 is stably localized in the cytoplasm. Functionally, circPKT2 promoted the HCC cells proliferation, migration, and invasion both in vitro and vivo. Mechanistically, circPTK2 was found to positively regulates the expression of AKR1C3 by acting as a sponge for miR-379-5p. Inhibition of miR-379-5p significantly mitigates the biological effects induced by circPTK2. AKR1C3 is identified as a direct target of miR-379-5p, and silencing AKR1C3 overturns the promotion progression effects of miR-379-5p inhibitor. In conclusion, our results revealed that circPTK2 facilitates the malignant progression of HCC via sponging miR-379-5p to up-regulate AKR1C3 expression. |
| format | Article |
| id | doaj-art-081859c4afd24fbb95d7bd3190b9ac69 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-081859c4afd24fbb95d7bd3190b9ac692025-01-12T12:19:05ZengNature PortfolioScientific Reports2045-23222025-01-0115111910.1038/s41598-025-85737-1hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5pShenglan Huang0Kan Liu1Yongkan Xu2Hua Wang3Shumin Fu4Jianbing Wu5Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityAbstract Circular RNAs (circRNAs) are widely involved in diverse biological processes of cancers. Nonetheless, the potential function of hsa_circ_0008305 in hepatocellular carcinoma (HCC) remains largely unknown. This study aims to elucidate the role and underlying mechanism of hsa_circ_0008305 in HCC. Our findings reveal that the novel circRNA hsa_circ_0008305 (circPTK2) is significantly upregulated in HCC tissues, with its elevated expression being positively correlated with advanced tumor T stage and vascular invasion. The circular characteristics and subcellular localization of hsa_circ_0008305 was determined by RNase R treatment and RNA nucleocytoplasmic separation. Further functional assays, including CCK8, EdU, colony formation assays, scratch-healing, transwell assays, and Xenograft tumor models were conducted to explore the biological functions of circPTK2. The regulatory mechanisms of circPTK2 were elucidated through RNA sequencing, enrichment analysis, and dual luciferase reporter assay. Our findings indicate that circPTK2 is stably localized in the cytoplasm. Functionally, circPKT2 promoted the HCC cells proliferation, migration, and invasion both in vitro and vivo. Mechanistically, circPTK2 was found to positively regulates the expression of AKR1C3 by acting as a sponge for miR-379-5p. Inhibition of miR-379-5p significantly mitigates the biological effects induced by circPTK2. AKR1C3 is identified as a direct target of miR-379-5p, and silencing AKR1C3 overturns the promotion progression effects of miR-379-5p inhibitor. In conclusion, our results revealed that circPTK2 facilitates the malignant progression of HCC via sponging miR-379-5p to up-regulate AKR1C3 expression.https://doi.org/10.1038/s41598-025-85737-1Hepatocellular carcinomaHsa_circ_0008305miR-379-5pAKR1C3Tumor progression |
| spellingShingle | Shenglan Huang Kan Liu Yongkan Xu Hua Wang Shumin Fu Jianbing Wu hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p Scientific Reports Hepatocellular carcinoma Hsa_circ_0008305 miR-379-5p AKR1C3 Tumor progression |
| title | hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p |
| title_full | hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p |
| title_fullStr | hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p |
| title_full_unstemmed | hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p |
| title_short | hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p |
| title_sort | hsa circ 0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating akr1c3 expression and sponging mir 379 5p |
| topic | Hepatocellular carcinoma Hsa_circ_0008305 miR-379-5p AKR1C3 Tumor progression |
| url | https://doi.org/10.1038/s41598-025-85737-1 |
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