第10卷，第3期

LncMIR31HG acts as a host gene for miR-31, also known as LncHIFCAR (long non-coding HIF-1 co-activating RNA), whose deregulation has been reported to promote the development of various human cancers, including lung cancer, colorectal cancer, etc. However, the biological functions and molecular mechanisms of MIR31HG in gastric cancer are unclear. The lncRNA MIR31HG was identified as a possible therapeutic target for gastric cancer throughout our work. In summary, we found that MIR31HG plays an oncogene role in gastric cancer; the deletion of MIR31HG significantly reduced gastric cancer cell proliferation, metastasis, and sphereforming ability; and the overexpression of MIR31HG promoted these capacities. FH535, a small molecule targeting β-catenin, was utilized to confirm that MIR31HG, which directs the malignant progression of gastric cancer, is β-catenin dependent. We revealed that MIR31HG positively regulated β-catenin stability by reducing β-catenin ubiquitination and increasing β-catenin steady-state expression. Furthermore, this is the first time that MIR31HG has been shown to interact with the E3 ligase c-CBL (dendritic cell (DC) -specific defect of casitas B-lineage lymphoma), and that c-CBL is reported to be involved in regulating β-catenin ubiquitination in cancer cells. MIR31HG interacted with c-CBL and caused its instability to protect β-catenin stability. Thus, our study provided insights into the applicability of using the MIR31HG-c-CBL-β-catenin axis as a potential therapeutic target in gastric cancer.

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