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The Role Of MiR-149-3p In Pituitary Adenoma Cells

Posted on:2021-04-18Degree:MasterType:Thesis
Country:ChinaCandidate:M H LiFull Text:PDF
GTID:2404330605971583Subject:Pharmaceutical engineering
Abstract/Summary:PDF Full Text Request
Pituitary adenoma is a common intracranial tumor.Most pituitary adenoma cannot be metastasized,so it is considered to be a benign tumor.However,these benign tumors may be highly invasive and may result in death due to infiltration of local structures or the syndrome induced by excessive hormone secretion.A large number of studies have shown that although small non-coding RNAs such as microRNAs cannot directly encode proteins,they play an important role in the growth process of living organisms.MicroRNAs have also been reported to regulate pituitary adenoma cells.In this project,we mainly proved that microRNA-149-3p(miR-149*)can promote the development of pituitary adenoma.Cell viability and apoptosis detection experiments showed that miR-149*promoted GH3 cell proliferation and inhibited TNF-?-induced apoptosis.Further research showed that miR-149*promoted cell proliferation by activating the AMPK signaling pathway.At the same time,miR-149*induced the conversion of LC3-I to LC3-? and the accumulation of p62,indicating that miR-149*induced the accumulation of autophagosomes by blocking autophagic flux.After inhibiting autophagy with 3-methyladenine(3-MA),miR-149*significantly reduced proliferative and apoptosis-inhibiting effects of GH3 cells.It shows that the pro-proliferation and apoptosis-inhibiting effects of miR-149*on cells depended to some extent on the start of autophagy induction.Further mechanistic studies indicated that miR-149*targeted PPP2R5A and inhibited the expression of PPP2R5A in GH3 cells to regulate cell proliferation,autophagy and apoptosis.In addition,miR-149*promoted tumorigenesis of GH3 cells in a nude mouse xenograft model.These data indicate that miR-149*,as an oncogene,can promote the growth of rat pituitary adenoma cells GH3 in vivo and in vitro,which may also provide a potential target for the effective treatment of pituitary adenoma.
Keywords/Search Tags:microRNA-149-3p, Pituitary adenoma, Autophagy, Apoptosis, AMPK signaling pathway
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