| First Author | Zhang S | Year | 2021 |
| Journal | Cell Death Dis | Volume | 13 |
| Issue | 1 | Pages | 25 |
| PubMed ID | 34934045 | Mgi Jnum | J:317482 |
| Mgi Id | MGI:6852810 | Doi | 10.1038/s41419-021-04470-5 |
| Citation | Zhang S, et al. (2021) Long noncoding RNA Meg3 sponges miR-708 to inhibit intestinal tumorigenesis via SOCS3-repressed cancer stem cells growth. Cell Death Dis 13(1):25 |
| abstractText | BACKGROUND: Colorectal cancer (CRC) remains the most common gastrointestinal cancer and a leading cause of cancer deaths worldwide, with most showing pathologies indicating the malignant transformation of early stage intestinal stem cells. The long non-coding RNA Meg3, which functions as a tumor suppressor, has been reported to be abnormal in multiple tumorigenesis events; however, the underlying mechanism by which Meg3 contributes to the malignant proliferation of colonic stem cells remains unclear. METHODS: We analyzed the expression levels of Meg3, miR-708, and SOCS3 in samples from Apc loss-of-function (Apc(min)) mice and patients with CRC, particularly in colonic crypt cells. Apc(min) mice and AMO/DSS-induced mice model (in vivo) and organoid culture system (in vitro) were used to explore the effect of the Meg3/miR-708/SOCS3 axis on tumorigenesis in the colon. In vitro, we performed RNApull-down, RNA immunoprecipitation, and luciferase reporter assays using DLD1 and RKO cell lines. FINDINGS: The Meg3/miR-708/SOCS3 signaling axis plays a critical role in the early stage of CRC development. Our data showed Meg3 levels negatively correlate with miR-708 levels both in clinical samples and in the Apc(min) mouse model, which indicated that Meg3 acts as a competitive endogenous RNA (ceRNA) of miR-708. Then, miR-708 served as an oncogene, inducing neoplasia in both Apc(min) mice and cultured colonic organoids. Put together, miR-708 appears to promote malignant proliferation of colonic stem cells by targeting SOCS3/STAT3 signaling. INTERPRETATION: These data revealed that Meg3 sponges miR-708 to inhibit CRC development via SOCS3-mediated repression of the malignant proliferation of colonic stem cells. The Meg3/miR-708/SOCS3 signaling axis provides potential targets for the diagnosis and treatment of CRC, particularly early stage CRC. |
