LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma
Sorafenib resistance is one of the main causes of poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) function as suppressors or oncogenic factors during tumor progression and drug resistance. Here, to identify therapeutic targets for HCC, the biolo...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402403353X |
| _version_ | 1797259708616146944 |
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| author | Kaixuan Xu Xinxin Wang Shuwei Hu Jiaxuan Tang Shihui Liu Hui Chen Xiaobin Zhang Penggao Dai |
| author_facet | Kaixuan Xu Xinxin Wang Shuwei Hu Jiaxuan Tang Shihui Liu Hui Chen Xiaobin Zhang Penggao Dai |
| author_sort | Kaixuan Xu |
| collection | DOAJ |
| description | Sorafenib resistance is one of the main causes of poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) function as suppressors or oncogenic factors during tumor progression and drug resistance. Here, to identify therapeutic targets for HCC, the biological mechanisms of abnormally expressed lncRNAs were examined in sorafenib-resistant HCC cells. Specifically, we established sorafenib-resistant HCC cell lines (Huh7-S and SMMC7721-S), which displayed an epithelial-mesenchymal transition (EMT) phenotype. Transcriptome sequencing (RNA-Seq) was performed to established differential lncRNA expression profiles for sorafenib-resistant cells. Through this analysis, we identified LINC00540 as significantly up-regulated in sorafenib-resistant cells and a candidate lncRNA for further mechanistic investigation. Functionally, LINC00540 knockdown promoted sorafenib sensitivity and suppressed migration, invasion, EMT and the activation of PI3K/AKT signaling pathway in sorafenib-resistant HCC cells, whereas overexpression of LINC00540 resulted in the opposite effects in parental cells. LINC00540 functions as a competing endogenous RNA (ceRNA) by competitively binding to miR-4677-3p , thereby promoting AKR1C2 expression. This is the first study that demonstrates a role for LINC00540 in enhancing sorafenib resistance, migration and invasion of HCC cells through the LINC00540/miR-4677-3p/AKR1C2 axis, suggesting that LINC00540 may represent a potential therapeutic target and prognosis biomarker for HCC. |
| first_indexed | 2024-03-07T16:53:01Z |
| format | Article |
| id | doaj.art-6171ecfd784046faa7065662065829cc |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:13:44Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-6171ecfd784046faa7065662065829cc2024-03-17T07:57:54ZengElsevierHeliyon2405-84402024-03-01105e27322LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinomaKaixuan Xu0Xinxin Wang1Shuwei Hu2Jiaxuan Tang3Shihui Liu4Hui Chen5Xiaobin Zhang6Penggao Dai7National Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, 710069, ChinaNational Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, 710069, ChinaNational Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, 710069, ChinaNational Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, 710069, ChinaNational Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, 710069, ChinaThe University Hospital of Northwest University, Xi'an, 710069, ChinaThe University Hospital of Northwest University, Xi'an, 710069, China; Corresponding author.National Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, 710069, China; Shaanxi Lifegen Co., Ltd, Xi'an, 712000, China; Corresponding author. National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, No.229, North Taibai Road, Beilin District, Xi'an, 710069, Shaanxi Province, China.Sorafenib resistance is one of the main causes of poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) function as suppressors or oncogenic factors during tumor progression and drug resistance. Here, to identify therapeutic targets for HCC, the biological mechanisms of abnormally expressed lncRNAs were examined in sorafenib-resistant HCC cells. Specifically, we established sorafenib-resistant HCC cell lines (Huh7-S and SMMC7721-S), which displayed an epithelial-mesenchymal transition (EMT) phenotype. Transcriptome sequencing (RNA-Seq) was performed to established differential lncRNA expression profiles for sorafenib-resistant cells. Through this analysis, we identified LINC00540 as significantly up-regulated in sorafenib-resistant cells and a candidate lncRNA for further mechanistic investigation. Functionally, LINC00540 knockdown promoted sorafenib sensitivity and suppressed migration, invasion, EMT and the activation of PI3K/AKT signaling pathway in sorafenib-resistant HCC cells, whereas overexpression of LINC00540 resulted in the opposite effects in parental cells. LINC00540 functions as a competing endogenous RNA (ceRNA) by competitively binding to miR-4677-3p , thereby promoting AKR1C2 expression. This is the first study that demonstrates a role for LINC00540 in enhancing sorafenib resistance, migration and invasion of HCC cells through the LINC00540/miR-4677-3p/AKR1C2 axis, suggesting that LINC00540 may represent a potential therapeutic target and prognosis biomarker for HCC.http://www.sciencedirect.com/science/article/pii/S240584402403353XHepatocellular carcinomaSorafenib resistanceLINC00540lncRNAsceRNAAKR1C2 |
| spellingShingle | Kaixuan Xu Xinxin Wang Shuwei Hu Jiaxuan Tang Shihui Liu Hui Chen Xiaobin Zhang Penggao Dai LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma Heliyon Hepatocellular carcinoma Sorafenib resistance LINC00540 lncRNAs ceRNA AKR1C2 |
| title | LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma |
| title_full | LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma |
| title_fullStr | LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma |
| title_full_unstemmed | LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma |
| title_short | LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma |
| title_sort | linc00540 promotes sorafenib resistance and functions as a cerna for mir 4677 3p to regulate akr1c2 in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Sorafenib resistance LINC00540 lncRNAs ceRNA AKR1C2 |
| url | http://www.sciencedirect.com/science/article/pii/S240584402403353X |
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