Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis
Abstract Background Melanoma is an aggressive tumor with a high mortality rate. Metformin, a commonly prescribed diabetes medication, has shown promise in cancer prevention and treatment. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA molecules that play a key role in tumor development by...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Cancer Cell International |
| Online Access: | https://doi.org/10.1186/s12935-024-03545-5 |
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| author | Kuo-Wang Tsai Jia-Bin Liao Hui-Wen Tseng |
| author_facet | Kuo-Wang Tsai Jia-Bin Liao Hui-Wen Tseng |
| author_sort | Kuo-Wang Tsai |
| collection | DOAJ |
| description | Abstract Background Melanoma is an aggressive tumor with a high mortality rate. Metformin, a commonly prescribed diabetes medication, has shown promise in cancer prevention and treatment. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA molecules that play a key role in tumor development by interacting with cellular chromatins. Despite the benefits of metformin, the anticancer mechanism underlying its effect on the regulation of lncRNAs in melanoma remains unclear. Methods We investigated the lncRNA profiles of human melanoma cells with and without metformin treatment using a next-generation sequencing approach (NGS). Utilizing public databases, we analyzed the expression levels and clinical impacts of LINC00094 and miR-1270 in melanoma. The expression levels of LINC00094 and miR-1270 were verified in human cell lines and clinical samples by real-time PCR and in situ hybridization. The biological roles of LINC00094 and miR-1270 in cell growth, proliferation, cell cycle, apoptosis, and motility were studied using in vitro assays. Results We identify a novel long noncoding RNA, namely LINC00094, whose expression considerably decreased in melanoma cells after metformin treatment. In situ hybridization analysis revealed substantially higher expression of LINC00094 in cutaneous melanoma tissue compared with adjacent normal epidermis and normal control tissues (P < 0.001). In nondiabetic patients with melanoma, the overall survival of high LINC00094 expression group was shorter than the low LINC00094 expression group with borderline statistical significance (log-rank test, P = 0.057). Coexpression analysis of LINC00094 indicated its involvement in the mitochondrial respiratory pathway, with its knockdown suppressing genes associated with mitochondrial oxidative phosphorylation, glycolysis, antioxidant production, and metabolite levels. Functional analysis revealed that silencing-LINC00094 inhibited the proliferation, colony formation, invasion, and migration of melanoma cells. Cell cycle analysis following LINC00094 knockdown revealed G1 phase arrest with reduced cell cycle protein expression. Combined TargetScan and reporter assays revealed a direct link between miR-1270 and LINC00094. Ectopic miR-1270 expression inhibited melanoma cell growth and motility while inducing apoptosis. Finally, through in silico analysis, we identified two miR-1270 target genes, CD276 and centromere protein M (CENPM), which may be involved in the biological functions of LINC00094. Conclusions Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, and targeting genes of CD276 and CENPM indicating its therapeutic potential in melanoma treatment. |
| format | Article |
| id | doaj-art-6f00cdd3497a414d8941ca68c146c0ec |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-6f00cdd3497a414d8941ca68c146c0ec2024-11-24T12:43:45ZengBMCCancer Cell International1475-28672024-11-0124112010.1186/s12935-024-03545-5Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axisKuo-Wang Tsai0Jia-Bin Liao1Hui-Wen Tseng2Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Pathology and Laboratory Medicine, Kaohsiung Veterans General HospitalDepartment of Dermatology, Ministry of Health and Welfare Pingtung HospitalAbstract Background Melanoma is an aggressive tumor with a high mortality rate. Metformin, a commonly prescribed diabetes medication, has shown promise in cancer prevention and treatment. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA molecules that play a key role in tumor development by interacting with cellular chromatins. Despite the benefits of metformin, the anticancer mechanism underlying its effect on the regulation of lncRNAs in melanoma remains unclear. Methods We investigated the lncRNA profiles of human melanoma cells with and without metformin treatment using a next-generation sequencing approach (NGS). Utilizing public databases, we analyzed the expression levels and clinical impacts of LINC00094 and miR-1270 in melanoma. The expression levels of LINC00094 and miR-1270 were verified in human cell lines and clinical samples by real-time PCR and in situ hybridization. The biological roles of LINC00094 and miR-1270 in cell growth, proliferation, cell cycle, apoptosis, and motility were studied using in vitro assays. Results We identify a novel long noncoding RNA, namely LINC00094, whose expression considerably decreased in melanoma cells after metformin treatment. In situ hybridization analysis revealed substantially higher expression of LINC00094 in cutaneous melanoma tissue compared with adjacent normal epidermis and normal control tissues (P < 0.001). In nondiabetic patients with melanoma, the overall survival of high LINC00094 expression group was shorter than the low LINC00094 expression group with borderline statistical significance (log-rank test, P = 0.057). Coexpression analysis of LINC00094 indicated its involvement in the mitochondrial respiratory pathway, with its knockdown suppressing genes associated with mitochondrial oxidative phosphorylation, glycolysis, antioxidant production, and metabolite levels. Functional analysis revealed that silencing-LINC00094 inhibited the proliferation, colony formation, invasion, and migration of melanoma cells. Cell cycle analysis following LINC00094 knockdown revealed G1 phase arrest with reduced cell cycle protein expression. Combined TargetScan and reporter assays revealed a direct link between miR-1270 and LINC00094. Ectopic miR-1270 expression inhibited melanoma cell growth and motility while inducing apoptosis. Finally, through in silico analysis, we identified two miR-1270 target genes, CD276 and centromere protein M (CENPM), which may be involved in the biological functions of LINC00094. Conclusions Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, and targeting genes of CD276 and CENPM indicating its therapeutic potential in melanoma treatment.https://doi.org/10.1186/s12935-024-03545-5 |
| spellingShingle | Kuo-Wang Tsai Jia-Bin Liao Hui-Wen Tseng Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis Cancer Cell International |
| title | Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis |
| title_full | Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis |
| title_fullStr | Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis |
| title_full_unstemmed | Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis |
| title_short | Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis |
| title_sort | metformin regulates the proliferation and motility of melanoma cells by modulating the linc00094 mir 1270 axis |
| url | https://doi.org/10.1186/s12935-024-03545-5 |
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