Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathway
Backgrounds: Sorafenib-resistance leads to poor prognosis and high mortality in advanced hepatocellular carcinoma (HCC), and this study aims to investigate the functional role of a circular RNA ITCH (circITCH) in regulating the sorafenib-resistance of HCC and its underlying mechanisms. Methods: The...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Molecular and Cellular Probes |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0890850822000883 |
| _version_ | 1827909369439715328 |
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| author | Xiaodong Li Xuedong Yin Heyi Bao Chang Liu |
| author_facet | Xiaodong Li Xuedong Yin Heyi Bao Chang Liu |
| author_sort | Xiaodong Li |
| collection | DOAJ |
| description | Backgrounds: Sorafenib-resistance leads to poor prognosis and high mortality in advanced hepatocellular carcinoma (HCC), and this study aims to investigate the functional role of a circular RNA ITCH (circITCH) in regulating the sorafenib-resistance of HCC and its underlying mechanisms. Methods: The expression of circITCH in HCC tissues and cell lines were detected by performing quantitative real-time polymerase chain reaction. Sorafenib-resistant HCC cells were transfected with PLCDH-circITCH to upregulate circITCH and intervened with sorafenib, and MTT assay, flow cytometry and transwell assay were used to test the cell viability, apoptosis and migration ability, respectively. The downstream target of circITCH were explored by using bioinformatic analysis, dual luciferase reporter system and Western blot. Results: CircITCH was significantly down-regulated in HCC tissues and cell lines, compared with their normal counterparts. Especially, in contrast with the sorafenib-sensitive HCC cells, continuous sorafenib treatment decreased the expression levels of circITCH in the sorafenib-resistant HCC cells. Overexpression of circITCH increased sorafenib-sensitivity, promoted cell apoptosis and reduced cell migration abilities in the sorafenib-resistant HCC cells. Mechanically, circITCH elevated PTEN expression to inactivate the PI3K/Akt signals through negatively regulating miR-20b-5p in HCC, and upregulating miR-20b-5p or inhibiting PTEN abolished the enhancing effect of circITCH overexpression on sorafenib-induced cytotoxicity in sorafenib-resistant HCC cells. Conclusion: Taken together, this study proves that circITCH enhances sorafenib-sensitivity in sorafenib-resistant HCC cells via regulating the miR-20b-5p/PTEN/PI3K/Akt signaling cascade, which highlights the potential value of circITCH as a target for enhancing the sorafenib-sensitivity in HCC. |
| first_indexed | 2024-03-13T01:37:10Z |
| format | Article |
| id | doaj.art-b39df4b0259141dfb9cf2d9c764e269f |
| institution | Directory Open Access Journal |
| issn | 0890-8508 |
| language | English |
| last_indexed | 2024-03-13T01:37:10Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular and Cellular Probes |
| spelling | doaj.art-b39df4b0259141dfb9cf2d9c764e269f2023-07-04T05:09:06ZengElsevierMolecular and Cellular Probes0890-85082023-02-0167101877Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathwayXiaodong Li0Xuedong Yin1Heyi Bao2Chang Liu3Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, ChinaDepartment of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, ChinaDepartment of General Surgery, Qiqihar First Hospital, Qiqihar, 161005, ChinaDepartment of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Corresponding author. Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, Yiyuan street, Nangang District, Harbin, 150001, Heilongjiang, China.Backgrounds: Sorafenib-resistance leads to poor prognosis and high mortality in advanced hepatocellular carcinoma (HCC), and this study aims to investigate the functional role of a circular RNA ITCH (circITCH) in regulating the sorafenib-resistance of HCC and its underlying mechanisms. Methods: The expression of circITCH in HCC tissues and cell lines were detected by performing quantitative real-time polymerase chain reaction. Sorafenib-resistant HCC cells were transfected with PLCDH-circITCH to upregulate circITCH and intervened with sorafenib, and MTT assay, flow cytometry and transwell assay were used to test the cell viability, apoptosis and migration ability, respectively. The downstream target of circITCH were explored by using bioinformatic analysis, dual luciferase reporter system and Western blot. Results: CircITCH was significantly down-regulated in HCC tissues and cell lines, compared with their normal counterparts. Especially, in contrast with the sorafenib-sensitive HCC cells, continuous sorafenib treatment decreased the expression levels of circITCH in the sorafenib-resistant HCC cells. Overexpression of circITCH increased sorafenib-sensitivity, promoted cell apoptosis and reduced cell migration abilities in the sorafenib-resistant HCC cells. Mechanically, circITCH elevated PTEN expression to inactivate the PI3K/Akt signals through negatively regulating miR-20b-5p in HCC, and upregulating miR-20b-5p or inhibiting PTEN abolished the enhancing effect of circITCH overexpression on sorafenib-induced cytotoxicity in sorafenib-resistant HCC cells. Conclusion: Taken together, this study proves that circITCH enhances sorafenib-sensitivity in sorafenib-resistant HCC cells via regulating the miR-20b-5p/PTEN/PI3K/Akt signaling cascade, which highlights the potential value of circITCH as a target for enhancing the sorafenib-sensitivity in HCC.http://www.sciencedirect.com/science/article/pii/S0890850822000883Circular ITCHPTENmiR-20b-5pHepatocellular carcinomaSorafenib resistance |
| spellingShingle | Xiaodong Li Xuedong Yin Heyi Bao Chang Liu Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathway Molecular and Cellular Probes Circular ITCH PTEN miR-20b-5p Hepatocellular carcinoma Sorafenib resistance |
| title | Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathway |
| title_full | Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathway |
| title_fullStr | Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathway |
| title_full_unstemmed | Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathway |
| title_short | Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and modulating the downstream PTEN-PI3K/Akt pathway |
| title_sort | circular rna itch increases sorafenib sensitivity in hepatocellular carcinoma via sequestering mir 20b 5p and modulating the downstream pten pi3k akt pathway |
| topic | Circular ITCH PTEN miR-20b-5p Hepatocellular carcinoma Sorafenib resistance |
| url | http://www.sciencedirect.com/science/article/pii/S0890850822000883 |
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