MiR-134-5p/Stat3 Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating Pvt1 Expression

作者全名："Liu, Dongrong; Liu, Yan; Hu, Yun; Ming, Ye; Meng, Xuehuan; Tan, Hao; Zheng, Leilei"

作者地址："[Liu, Dongrong; Liu, Yan; Hu, Yun; Ming, Ye; Meng, Xuehuan; Tan, Hao; Zheng, Leilei] Chongqing Med Univ, Affiliated Stomatol Hosp, Chongqing 401147, Peoples R China; [Liu, Dongrong] Second Peoples Hosp Yibin, Dept Stomatol, Yibin 644000, Peoples R China; [Liu, Yan] Chongqing Med Univ, Affiliated Hosp 2, Dept Stomatol, Chongqing 400010, Peoples R China; [Hu, Yun; Ming, Ye; Meng, Xuehuan; Tan, Hao; Zheng, Leilei] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 401147, Peoples R China; [Hu, Yun; Ming, Ye; Meng, Xuehuan; Tan, Hao; Zheng, Leilei] Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing 401147, Peoples R China"

通信作者："Zheng, LL (通讯作者)，Chongqing Med Univ, Affiliated Stomatol Hosp, Chongqing 401147, Peoples R China.; Zheng, LL (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 401147, Peoples R China.; Zheng, LL (通讯作者)，Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing 401147, Peoples R China."

来源：LIFE-BASEL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000875064800001

JCR分区：Q2

影响因子：3.2

年份：2022

卷号：12

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：MSCs; proliferation; migration; miR-134-5p; Stat3; Pvt1

摘要："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 Stat3 in this process. The results showed that co-cultured MSCs significantly exhibited enhanced tumorigenic, migratory, and proliferative abilities. Both up-regulation of Stat3 and down-regulation of miR-134-5p were detected in co-cultured MSCs. Furthermore, miR-134-5p directly regulated Stat3 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 Stat3 gain-of-function treatment reversed these effects. In addition, Pvt1 was confirmed to be regulated by miR-134-5p through Stat3 and the suppression of Pvt1 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 Stat3, highlighting a crucial role of loss-of-function of miR-134-5p/Stat3 axis in the malignant transformation, providing a reference to the potential clinic use of MSCs."

基金机构："National Natural Science Foundation of China [81470772]; Medical Scientific Research Project of Chongqing [cstc2020jcyj-msxmX0307, 2018ZDXM020]"

基金资助正文："This study was supported by the National Natural Science Foundation of China [No.: 81470772] and Medical Scientific Research Project of Chongqing [No.: cstc2020jcyj-msxmX0307, 2018ZDXM020]."