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长非编码 RNA 父系表达基因 10 的下调通过介导 microRNA-33a 抑制 A375 细胞的增殖、迁移和侵袭。

Declination of long noncoding RNA paternally expressed gene 10 inhibits A375 cells proliferation, migration, and invasion via mediating microRNA-33a.

机构信息

Department of Dermatology, Binzhou People's Hospital, Binzhou, China.

Department of Oncology, Binzhou People's Hospital, Binzhou, China.

出版信息

J Cell Biochem. 2019 Dec;120(12):19868-19877. doi: 10.1002/jcb.29292. Epub 2019 Jul 18.

Abstract

The importance of long noncoding RNAs (lncRNAs) has been certified in malignant melanoma. Nonetheless, the functions of lncRNA paternally expressed gene 10 (PEG10) in malignant melanoma remain uninvestigated. This research discloses the influence of PEG10 in the biological actions of malignant melanoma cells. The sh-PEG10 plasmid was transfected into A375 cells; meanwhile, the effects of declined PEG10 on cell viability, apoptosis, migration, invasion, and the correlative protein levels were probed. The miR-33a expression in sh-PEG10-transfected cells was examined, and the above biological processes were studied again in miR-33a inhibitor-transfected A375 cells. Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mechanistic target of rapamycin (mTOR) pathways were delved via Western blot. We found that the enhancement of PEG10 was discovered in melanoma tissues compared to related nonmelanoma tissues. Declination of PEG10 frustrated cell viability, repressed cyclinD1 and CDK4 expression, and triggered apoptosis, as well as suppressed migration and invasion in A375 cells. A negative correction between PEG10 and miR-33a was confirmed, and repressed miR-33a inverted the functions of PEG10 repression in A375 cells. In addition, PEG10 repression discouraged the activation of PI3K/AKT and mTOR pathways via elevation of miR-33a. These results indicated that declination of PEG10 restrained A375 cell growth, migration, and invasion via adjusting miR-33a and PI3K/AKT and mTOR pathways.

摘要

长链非编码 RNA(lncRNA)在恶性黑色素瘤中的重要性已得到证实。然而,lncRNA 父系表达基因 10(PEG10)在恶性黑色素瘤中的功能仍未被研究。本研究揭示了 PEG10 在恶性黑色素瘤细胞生物学行为中的影响。sh-PEG10 质粒转染 A375 细胞;同时,研究了 PEG10 下调对细胞活力、凋亡、迁移、侵袭和相关蛋白水平的影响。检测了 sh-PEG10 转染细胞中 miR-33a 的表达,然后在转染 miR-33a 抑制剂的 A375 细胞中再次研究了上述生物学过程。通过 Western blot 研究了磷脂酰肌醇 3-激酶/蛋白激酶 B(PI3K/AKT)和雷帕霉素靶蛋白(mTOR)途径。我们发现与相关非黑色素瘤组织相比,黑色素瘤组织中 PEG10 的表达增强。PEG10 下调抑制了 A375 细胞的活力,抑制了 cyclinD1 和 CDK4 的表达,触发了凋亡,并抑制了细胞的迁移和侵袭。证实了 PEG10 和 miR-33a 之间存在负相关,抑制 miR-33a 反转了 PEG10 抑制 A375 细胞功能的作用。此外,PEG10 下调通过升高 miR-33a 抑制了 PI3K/AKT 和 mTOR 途径的激活。这些结果表明,PEG10 下调通过调节 miR-33a 和 PI3K/AKT 和 mTOR 途径抑制 A375 细胞的生长、迁移和侵袭。

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