MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> Expression
Mesenchymal stem cells (MSCs) are critical in regenerating tissues because they can differentiate into various tissue cells. MSCs interact closely with cells in the tissue microenvironment during the repair of damaged tissue. Although regarded as non-healing wounds, tumors can be treated by MSCs, wh...
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MDPI AG
2022-10-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/10/1648 |
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| author | Dongrong Liu Yan Liu Yun Hu Ye Ming Xuehuan Meng Hao Tan Leilei Zheng |
| author_facet | Dongrong Liu Yan Liu Yun Hu Ye Ming Xuehuan Meng Hao Tan Leilei Zheng |
| author_sort | Dongrong Liu |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) are critical in regenerating tissues because they can differentiate into various tissue cells. MSCs interact closely with cells in the tissue microenvironment during the repair of damaged tissue. Although regarded as non-healing wounds, tumors can be treated by MSCs, which showed satisfactory treatment outcomes in previous reports. However, it is largely unknown whether the biological behaviors of MSCs would be affected by the tumor microenvironment. Exploring the truth of tumor microenvironmental cues driving MSCs tumor “wound” regeneration would provide a deeper understanding of the biological behavior of MSCs. Therefore, we mimicked the tumor microenvironment using co-cultured glioma C6 cells and rat MSCs, aiming to assess the proliferation and migration of MSCs and the associated effects of <i>Stat3</i> in this process. The results showed that co-cultured MSCs significantly exhibited enhanced tumorigenic, migratory, and proliferative abilities. Both up-regulation of <i>Stat3</i> and down-regulation of miR-134-5p were detected in co-cultured MSCs. Furthermore, miR-134-5p directly regulated <i>Stat3</i> by binding to the sequence complementary to microRNA response elements in the 3′-UTR of its mRNA. Functional studies showed that both the migration and proliferation abilities of co-cultured MSCs were inhibited by miR-134-5p, whereas <i>Stat3</i> gain-of-function treatment reversed these effects. In addition, <i>Pvt1</i> was confirmed to be regulated by miR-134-5p through <i>Stat3</i> and the suppression of <i>Pvt1</i> reduced the migration and proliferation abilities of co-cultured MSCs. To sum up, these results demonstrate a suppressive role of miR-134-5p in tumor-environment-driven malignant transformation of rat MSCs through directly targeting <i>Stat3</i>, highlighting a crucial role of loss-of-function of miR-134-5p/<i>Stat3</i> axis in the malignant transformation, providing a reference to the potential clinic use of MSCs. |
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| spelling | doaj.art-51ee1e9e9f844f7fa8d948b0b07c9c442023-11-24T00:57:52ZengMDPI AGLife2075-17292022-10-011210164810.3390/life12101648MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> ExpressionDongrong Liu0Yan Liu1Yun Hu2Ye Ming3Xuehuan Meng4Hao Tan5Leilei Zheng6The Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, ChinaThe Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, ChinaThe Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, ChinaThe Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, ChinaThe Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, ChinaThe Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, ChinaThe Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, ChinaMesenchymal stem cells (MSCs) are critical in regenerating tissues because they can differentiate into various tissue cells. MSCs interact closely with cells in the tissue microenvironment during the repair of damaged tissue. Although regarded as non-healing wounds, tumors can be treated by MSCs, which showed satisfactory treatment outcomes in previous reports. However, it is largely unknown whether the biological behaviors of MSCs would be affected by the tumor microenvironment. Exploring the truth of tumor microenvironmental cues driving MSCs tumor “wound” regeneration would provide a deeper understanding of the biological behavior of MSCs. Therefore, we mimicked the tumor microenvironment using co-cultured glioma C6 cells and rat MSCs, aiming to assess the proliferation and migration of MSCs and the associated effects of <i>Stat3</i> in this process. The results showed that co-cultured MSCs significantly exhibited enhanced tumorigenic, migratory, and proliferative abilities. Both up-regulation of <i>Stat3</i> and down-regulation of miR-134-5p were detected in co-cultured MSCs. Furthermore, miR-134-5p directly regulated <i>Stat3</i> by binding to the sequence complementary to microRNA response elements in the 3′-UTR of its mRNA. Functional studies showed that both the migration and proliferation abilities of co-cultured MSCs were inhibited by miR-134-5p, whereas <i>Stat3</i> gain-of-function treatment reversed these effects. In addition, <i>Pvt1</i> was confirmed to be regulated by miR-134-5p through <i>Stat3</i> and the suppression of <i>Pvt1</i> reduced the migration and proliferation abilities of co-cultured MSCs. To sum up, these results demonstrate a suppressive role of miR-134-5p in tumor-environment-driven malignant transformation of rat MSCs through directly targeting <i>Stat3</i>, highlighting a crucial role of loss-of-function of miR-134-5p/<i>Stat3</i> axis in the malignant transformation, providing a reference to the potential clinic use of MSCs.https://www.mdpi.com/2075-1729/12/10/1648MSCsproliferationmigrationmiR-134-5p<i>Stat3</i><i>Pvt1</i> |
| spellingShingle | Dongrong Liu Yan Liu Yun Hu Ye Ming Xuehuan Meng Hao Tan Leilei Zheng MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> Expression Life MSCs proliferation migration miR-134-5p <i>Stat3</i> <i>Pvt1</i> |
| title | MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> Expression |
| title_full | MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> Expression |
| title_fullStr | MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> Expression |
| title_full_unstemmed | MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> Expression |
| title_short | MiR-134-5p/<i>Stat3</i> Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating <i>Pvt1</i> Expression |
| title_sort | mir 134 5p i stat3 i axis modulates proliferation and migration of mscs co cultured with glioma c6 cells by regulating i pvt1 i expression |
| topic | MSCs proliferation migration miR-134-5p <i>Stat3</i> <i>Pvt1</i> |
| url | https://www.mdpi.com/2075-1729/12/10/1648 |
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