miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2
ABSTRACTMetabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR wa...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Cancer Biology & Therapy |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2024.2315651 |
| _version_ | 1797299378951553024 |
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| author | Mingzhi Xia Jie Chen Yingyun Hu Bin Qu Qianqian Bu Haoming Shen |
| author_facet | Mingzhi Xia Jie Chen Yingyun Hu Bin Qu Qianqian Bu Haoming Shen |
| author_sort | Mingzhi Xia |
| collection | DOAJ |
| description | ABSTRACTMetabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR was used to determine miR-10b-5p and SCL38A2 expression levels. IHC, WB, and TUNEL assays were used to assess the proliferation and apoptosis of the tissues. The proliferation, migration, invasion, and apoptosis of PLC cells were determined using the CCK-8 assay, Transwell assay, and flow cytometry. The interaction between miR-10b-5p and SLC38A2 was determined using dual-luciferase reporter assay. A PLC xenograft model in BALB/c nude mice was established, and tumorigenicity and SLC38A2 expression were estimated. Finally, liquid chromatography – mass spectrometry (LC-MS) untargeted metabolomics was used to analyze the metabolic profiles of xenograft PLC tissues in nude mice. miR-10b-5p was a key molecule in the regulation of PLC. Compared with para-carcinoma tissues, miR-10b-5p expression was increased in tumor tissues. miR-10b-5p facilitated proliferation, migration, and invasion of PLC cells. Mechanistically, miR-10b-5p targeted SLC38A2 to promote PLC tumor growth. Additionally, miR-10b-5p altered the metabolic features of PLC in vivo. Overexpression of miR-10b-5p resulted in remarkably higher amounts of lumichrome, folic acid, octanoylcarnitine, and Beta-Nicotinamide adenine dinucleotide, but lower levels of 2-methylpropanal, glycyl-leucine, and 2-hydroxycaproic acid. miR-10b-5p facilitates the metabolic reprogramming of PLC by targeting SLC38A2, which ultimately boosts the proliferation, migration, and invasion of PLC cells. Therefore, miR-10b-5p and SLC38A2 are potential targets for PLC diagnosis and treatment. |
| first_indexed | 2024-03-07T22:49:43Z |
| format | Article |
| id | doaj.art-ba70637180df47d5bea3ff7e8d2cce37 |
| institution | Directory Open Access Journal |
| issn | 1538-4047 1555-8576 |
| language | English |
| last_indexed | 2024-03-07T22:49:43Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj.art-ba70637180df47d5bea3ff7e8d2cce372024-02-23T11:22:23ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2315651miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2Mingzhi Xia0Jie Chen1Yingyun Hu2Bin Qu3Qianqian Bu4Haoming Shen5Breast Surgery Department I, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. ChinaLiver and gallbladder surgery Department I, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. ChinaHunan Cancer Prevention and Control Office, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. ChinaDepartment of Clinical Laboratory, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. ChinaDepartment of Clinical Laboratory, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. ChinaDepartment of Clinical Laboratory, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. ChinaABSTRACTMetabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR was used to determine miR-10b-5p and SCL38A2 expression levels. IHC, WB, and TUNEL assays were used to assess the proliferation and apoptosis of the tissues. The proliferation, migration, invasion, and apoptosis of PLC cells were determined using the CCK-8 assay, Transwell assay, and flow cytometry. The interaction between miR-10b-5p and SLC38A2 was determined using dual-luciferase reporter assay. A PLC xenograft model in BALB/c nude mice was established, and tumorigenicity and SLC38A2 expression were estimated. Finally, liquid chromatography – mass spectrometry (LC-MS) untargeted metabolomics was used to analyze the metabolic profiles of xenograft PLC tissues in nude mice. miR-10b-5p was a key molecule in the regulation of PLC. Compared with para-carcinoma tissues, miR-10b-5p expression was increased in tumor tissues. miR-10b-5p facilitated proliferation, migration, and invasion of PLC cells. Mechanistically, miR-10b-5p targeted SLC38A2 to promote PLC tumor growth. Additionally, miR-10b-5p altered the metabolic features of PLC in vivo. Overexpression of miR-10b-5p resulted in remarkably higher amounts of lumichrome, folic acid, octanoylcarnitine, and Beta-Nicotinamide adenine dinucleotide, but lower levels of 2-methylpropanal, glycyl-leucine, and 2-hydroxycaproic acid. miR-10b-5p facilitates the metabolic reprogramming of PLC by targeting SLC38A2, which ultimately boosts the proliferation, migration, and invasion of PLC cells. Therefore, miR-10b-5p and SLC38A2 are potential targets for PLC diagnosis and treatment.https://www.tandfonline.com/doi/10.1080/15384047.2024.2315651Primary liver cancertumorigenicitySLC38A2metabolic reprogramming |
| spellingShingle | Mingzhi Xia Jie Chen Yingyun Hu Bin Qu Qianqian Bu Haoming Shen miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2 Cancer Biology & Therapy Primary liver cancer tumorigenicity SLC38A2 metabolic reprogramming |
| title | miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2 |
| title_full | miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2 |
| title_fullStr | miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2 |
| title_full_unstemmed | miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2 |
| title_short | miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2 |
| title_sort | mir 10b 5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting slc38a2 |
| topic | Primary liver cancer tumorigenicity SLC38A2 metabolic reprogramming |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2024.2315651 |
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