Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p
Background. Hepatocellular carcinoma (HCC) is the most frequently occurring cancer and contributes to the largest number of cancer-associated deaths worldwide. Recent evidence suggests that circular RNAs (circRNAs), which are critical for HCC etiology and metastasis, are distinctly modulated in HCC....
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Wiley
2022-01-01
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| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2022/1206134 |
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| author | Rui Qiu Zhifeng Zeng |
| author_facet | Rui Qiu Zhifeng Zeng |
| author_sort | Rui Qiu |
| collection | DOAJ |
| description | Background. Hepatocellular carcinoma (HCC) is the most frequently occurring cancer and contributes to the largest number of cancer-associated deaths worldwide. Recent evidence suggests that circular RNAs (circRNAs), which are critical for HCC etiology and metastasis, are distinctly modulated in HCC. Nevertheless, the underlying mechanism of circRNA-mediated sorafenib resistance (SOR) in HCC is yet to be determined. Methods. The hsa_circ_0006988, IGF1, and miR-15a-5p contents were quantified via ELISA and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Cell Counting Kit-8 (CCK-8) was used for the IC50 evaluation. Lastly, associations among hsa_circ_0006988, IGF1, and miR-15a-5p were validated through dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays. Results. Herein, a new circRNA, hsa_circ_0006988, was identified, and its levels were markedly enhanced in SOR-resistant (SOR-R) HCC tissues. Functionally, hsa_circ_0006988 strongly suppressed SOR toxicity in vitro. Our examination of the signaling pathway revealed that hsa_circ_0006988 sequestered miR-15a-5p, a negative modulator of IGF1, thus suggesting that hsa_circ_0006988 deficiency diminished SOR resistance of HCC, and this action utilized the release of excess miR-15a-5p, which suppressed IGF1 levels. Moreover, miR-15a-5p overexpression reversed the hsa_circ_0006988-mediated SOR-R and enhanced IGF1 levels in HCC cells. Conclusion. Hsa_circ_0006988 partly promoted the SOR-R of HCC cells through miR-15a-5p sequestering and upregulation of IGF1 levels. |
| format | Article |
| id | doaj-art-c5ccad98f29644c4b510116f791c7c50 |
| institution | DOAJ |
| issn | 2291-2797 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj-art-c5ccad98f29644c4b510116f791c7c502025-08-20T03:22:42ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27972022-01-01202210.1155/2022/1206134Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5pRui Qiu0Zhifeng Zeng1Second General SurgerySecond General SurgeryBackground. Hepatocellular carcinoma (HCC) is the most frequently occurring cancer and contributes to the largest number of cancer-associated deaths worldwide. Recent evidence suggests that circular RNAs (circRNAs), which are critical for HCC etiology and metastasis, are distinctly modulated in HCC. Nevertheless, the underlying mechanism of circRNA-mediated sorafenib resistance (SOR) in HCC is yet to be determined. Methods. The hsa_circ_0006988, IGF1, and miR-15a-5p contents were quantified via ELISA and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Cell Counting Kit-8 (CCK-8) was used for the IC50 evaluation. Lastly, associations among hsa_circ_0006988, IGF1, and miR-15a-5p were validated through dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays. Results. Herein, a new circRNA, hsa_circ_0006988, was identified, and its levels were markedly enhanced in SOR-resistant (SOR-R) HCC tissues. Functionally, hsa_circ_0006988 strongly suppressed SOR toxicity in vitro. Our examination of the signaling pathway revealed that hsa_circ_0006988 sequestered miR-15a-5p, a negative modulator of IGF1, thus suggesting that hsa_circ_0006988 deficiency diminished SOR resistance of HCC, and this action utilized the release of excess miR-15a-5p, which suppressed IGF1 levels. Moreover, miR-15a-5p overexpression reversed the hsa_circ_0006988-mediated SOR-R and enhanced IGF1 levels in HCC cells. Conclusion. Hsa_circ_0006988 partly promoted the SOR-R of HCC cells through miR-15a-5p sequestering and upregulation of IGF1 levels.http://dx.doi.org/10.1155/2022/1206134 |
| spellingShingle | Rui Qiu Zhifeng Zeng Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p Canadian Journal of Gastroenterology and Hepatology |
| title | Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p |
| title_full | Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p |
| title_fullStr | Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p |
| title_full_unstemmed | Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p |
| title_short | Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p |
| title_sort | hsa circ 0006988 promotes sorafenib resistance of hepatocellular carcinoma by modulating igf1 using mir 15a 5p |
| url | http://dx.doi.org/10.1155/2022/1206134 |
| work_keys_str_mv | AT ruiqiu hsacirc0006988promotessorafenibresistanceofhepatocellularcarcinomabymodulatingigf1usingmir15a5p AT zhifengzeng hsacirc0006988promotessorafenibresistanceofhepatocellularcarcinomabymodulatingigf1usingmir15a5p |