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  • Title: MicroRNA-329 inhibits cell proliferation and tumor growth while facilitates apoptosis via negative regulation of KDM1A in gastric cancer.
    Author: Cai L, Chen Q, Fang S, Lian M, Cai M.
    Journal: J Cell Biochem; 2018 Apr; 119(4):3338-3351. PubMed ID: 29130516.
    Abstract:
    Altered expression of microRNA (miRNA) is strongly implicated in gastric cancer (GC). Here, we demonstrated a decreased expression of miRNA-329 in GC. Then we explored the regulatory mechanisms responsible for its effect on GC cells. GC tissues and their adjacent non-tumor tissues were collected. Complete follow-up was updated. A series of inhibitors, mimics, and siRNA against KDM1A were introduced to validate regulatory mechanisms for miR-497 and KDM1A in BGC-823 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were employed for evaluating the expressions of miRNA-329, KDM1A, H3K4me1, and H3K4me2. Cell proliferation, cycle progression, and apoptosis were assessed by means of an MTT assay and flow cytometry. Cell colony formation was assessed. uman gastric cancer xenotransplanted into nude mice was studied. As opposed to adjacent tissues and gastritis tissues, miRNA-329 was highly expressed and KDM1A was low expressed in GC tissues. The patients with high miRNA-329 expression or low KDM1A expression had longer survival periods. The miRNA-329 mimics and siRNA against KDM1A decreased KDM1A expression and increased H3K4me1 and H3K4me2 expressions. Forced expression of miRNA-329 in gastric cancer cells significantly promotes their capacity of apoptosis but reduces proliferation, migration, and invasion. KDM1A is a direct downstream target for miRNA-329. In a nude mouse subcutaneous tumor system, in vivo tumor growth of BGC-823 was significantly inhibited after treatment of miRNA-329 mimics or siRNA against KDM1A. We conclude that miRNA-329 functions as a tumor suppressor in GC, which could be achieved via transcriptional suppression of KDM1A.
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