Involvement of EGFR, ERK-1,2 and AKT-1,2 Activity on Human Glioma Cell Growth.
Involvement of EGFR, ERK-1,2 and AKT-1,2 Activity on Human Glioma Cell Growth.
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DOI：
10.31557/apjcp.2020.21.12.3469
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发表时间：
2020-12-01
期刊：
影响因子：
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通讯作者：
Ebrahimi-Barough S
中科院分区：
文献类型：
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作者：
Alahverdi A;Arefian E;Soleimani M;Ai J;Yousefi-Ahmadipour A;Babaei A;Islam MS;Ebrahimi-Barough S
多形性胶质母细胞瘤（GBM）是最常见和最致命的原发性脑肿瘤。基因治疗是有前途的方法之一，涉及递送用于特异性抗肿瘤反应/活性的遗传治疗分子。miRNAs可以通过调控基因表达来调节细胞的生物学功能，包括复制、细胞生长和凋亡。在这项研究中，我们发现miR-4731的表达下调发生在GBM细胞中。我们进一步确定miR-4731通过抑制GBM细胞增殖而表现为肿瘤抑制因子。我们进一步研究了miR-4731和EGFR、ERK-1，2和AKT-1，2在GBM细胞系U87和U251中的分子机制。miR-4731的体外异位表达影响U87和U251细胞的增殖、迁移和侵袭。荧光素酶报告基因测定验证了miR-4731靶向EGFR的3 '非翻译区（3'-UTR）。结论：miR-4731通过靶向EGFR表达，在GBM细胞增殖和迁移中发挥抑癌作用，miR-4731可能成为GBM早期诊断或治疗的新靶点。
GBM (Glioblastoma multiforme) is the most prevalent and lethal primary brain tumor. Gene therapy is one of the promising approaches and involves the delivery of genetic therapeutic molecules for specific antitumour response/activity. miRNAs can regulate the cell biology functions including replication, cell growth, and apoptosis by regulating gene expression. In this study, we found that down-regulation of miR-4731 expression occurred in GBM cells. We further determined that miR-4731 behaved as a tumor suppressor by inhibiting GBM cell proliferation. We further investigated the molecular mechanisms of miR-4731 and EGFR, ERK-1,2 and AKT-1,2 in GBM cell lines U87 and U251. The in vitro ectopic expression of miR-4731 affected cell proliferation, migration, and invasion of U87 and U251 cells. Luciferase reporter assays validated that miR-4731 targeted the 3′-untranslated region (3′-UTR) of EGFR. In conclusions, we identified that miR-4731 plays a tumor suppressor role in GBM cell proliferation and migration by targeting EGFR expression, and miR-4731 may act as a novel biomarker for early diagnosis or therapeutic target of GBM.