Gastrointestinal Peritoneal Cancer Surgery, The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine, 1 Fuhua Road, Futian District, Shenzhen, 518033, Guangdong, China.
Shenzhen Traditional Chinese Medicine Hospital, 1 Fuhua Road, Futian District, Shenzhen, 518033, Guangdong, China.
Mol Neurobiol. 2022 Jan;59(1):47-60. doi: 10.1007/s12035-021-02431-9. Epub 2021 Oct 8.
Mesenchymal stem cell-derived extracellular vesicles (MSC-EV) can transport microRNAs (miRNAs) into colorectal cancer (CRC) cells, thus to inhibit the malignant phenotype of cancer cells. Whether MSC-EV could deliver miR-34a-5p to suppress CRC development was surveyed through the research. miR-34a-5p, c-MYC, DNA methyltransferase 3a (DNMT3a), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression were measured in CRC tissues and cell lines. miR-34a-5p and c-MYC expression were altered by transfection in HCT-116 cells. MSC-EV were transfected with miR-34a-5p- and c-MYC-related oligonucleotides and co-cultured with HCT-116 cells. HCT-116 cell growth after treatment was observed. Furthermore, the functional roles of miR-34a-5p and c-MYC were explored in vivo. The combined interactions of miR-34a-5p/c-MYC/DNMT3a/PTEN axis were assessed. miR-34a-5p and PTEN were downregulated while c-MYC and DNMT3a were upregulated in CRC. Depletion of miR-34a-5p drove while that of c-MYC restricted CRC cell growth. MSC-EV retarded CRC progression. Moreover, MSC-EV carrying overexpressed miR-34a-5p or depleted c-MYC further disrupted CRC cell progression. miR-34a-5p targeted c-MYC to regulate DNMT3a and PTEN. c-MYC overexpression abrogated EV-derived miR-34a-5p upregulation-induced effects on CRC. Restoring miR-34a-5p or depleting c-MYC in MSC-EV limited CRC tumor formation. MSC-EV-derived miR-34a-5p depresses CRC development through modulating the binding of c-MYC to DNMT3a and epigenetically regulating PTEN.
间充质干细胞衍生的细胞外囊泡 (MSC-EV) 可将 microRNAs (miRNAs) 转运至结直肠癌细胞 (CRC)，从而抑制癌细胞的恶性表型。通过研究调查了 MSC-EV 是否可以递送 miR-34a-5p 以抑制 CRC 发展。在 CRC 组织和细胞系中测量了 miR-34a-5p、c-MYC、DNA 甲基转移酶 3a (DNMT3a) 和 10 号染色体缺失的磷酸酶和张力蛋白同源物 (PTEN) 的表达。通过转染在 HCT-116 细胞中改变 miR-34a-5p 和 c-MYC 的表达。用 miR-34a-5p 和 c-MYC 相关的寡核苷酸转染 MSC-EV，并与 HCT-116 细胞共培养。观察处理后 HCT-116 细胞的生长情况。此外，还在体内探索了 miR-34a-5p 和 c-MYC 的功能作用。评估了 miR-34a-5p/c-MYC/DNMT3a/PTEN 轴的联合相互作用。在 CRC 中下调 miR-34a-5p 和 PTEN，而上调 c-MYC 和 DNMT3a。miR-34a-5p 的耗竭促进了 CRC 细胞的生长，而 c-MYC 的耗竭则限制了 CRC 细胞的生长。MSC-EV 减缓了 CRC 的进展。此外，携带过表达 miR-34a-5p 或耗尽 c-MYC 的 MSC-EV 进一步破坏了 CRC 细胞的进展。miR-34a-5p 靶向 c-MYC 以调节 DNMT3a 和 PTEN。c-MYC 的过表达消除了 EV 衍生的 miR-34a-5p 上调对 CRC 的影响。在 MSC-EV 中恢复 miR-34a-5p 或耗尽 c-MYC 可限制 CRC 肿瘤的形成。MSC-EV 衍生的 miR-34a-5p 通过调节 c-MYC 与 DNMT3a 的结合并通过表观遗传调节 PTEN 来抑制 CRC 的发展。
