Search

Parkinson's disease (PD) is a common neurodegenerative disease. Various microRNAs (miRNAs) have been reported to play important roles in cell growth regulation and inflammatory reaction. However, the detailed roles of miR-217 and miR-138-5p in PD progression remain to be investigated. In the present study, we explored the effects and underlying mechanisms of miR-217 and miR-138-5p on the inflammatory response, oxidative stress and the induction of neuronal apoptosis in an in vitro PD cell line model induced by 1-methyl-4-phenylpyridinium (MPP + ). The results of the biological software analysis and luciferase reporter assays demonstrated that sirtuin 1 (SIRT1) was a direct target of miR-217 and miR-138-5p. MiR-217 and miR-138-5p exhibited a negative regulatory effect on the expression of SIRT1 in SH-SY5Y cells. In addition, the expression levels of miR-217 and miR-138-5p were increased, and SIRT1 expression was decreased in SH-SY5Y cells following MPP + treatment. Loss-of-function experiments indicated that treatment of the cells with inhibitors against miR-217 and miR-138-5p promoted cell viability and superoxide dismutase (SOD) activity, while the induction of cell apoptosis, lactate dehydrogenase (LDH) activity, and the reactive oxygen species (ROS) release were inhibited in MPP + -induced SH-SY5Y cells. Moreover, the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were reduced in MPP + -induced SH-SY5Y cells. Treatment of the cells with the miR-217 and the miR-138-5p inhibitors significantly inhibited the ratio of phosphorylated (p)-p65/p65 expression levels in MPP + -induced SH-SY5Y cells. In summary, the present study demonstrated that the miR-217/miR-138-5p/SIRT1 axis was involved in the progression of PD by regulating the inflammatory response and the induction of oxidative stress and neuronal apoptosis. The data provide new diagnostic and therapeutic strategies for PD patients., Competing Interests: None., (AJTR Copyright © 2019.)

Colorectal cancer (CRC) is the second most common cancer in the world. The incidence of this cancer is increasing in the developing countries. Mechanism of CRC tumorigenesis has been widely studied at the molecular levels, and has been recently proposed microRNAs as novel players in CRC. It has been reported that microRNA-138-5p (miR-138-5p) play key roles in different kinds of human cancers. However, the roles and underlying molecular mechanisms of miR-138-5p in CRC have not been adequately elucidated. Thus, the aim of the present study was to investigate the roles and possible regulatory mechanisms of miR-138-5p in CRC. In this study, we demonstrated that miR-138-5p was significantly down-regulated in CRC tissue samples and cell lines. Functional analyses indicated that the overexpression of miR-138-5p significantly delayed cell proliferation, reduced colony formation and increased apoptosis in CRC cell lines. Moreover, human telomerase reverse transcriptase (hTERT), an important oncogene in the management of tumors, was confirmed as a direct target of miR-138-5p in CRC cells. We also found that the hTERT expression was increased in CRC tissues and was inversely correlated with miR-138-5p. Further study showed that the restoration of hTERT expression by an overexpressing plasmid could reverse the effects of miR-138-5p on proliferation and apoptosis of CRC cells. Taken together, these data defines a major suppresses proliferation and promotes apoptosis role for miR-138-5p, a microRNA functions as a tumor suppressor in CRC, by directly targeting hTERT, which would be provide a new strategy for future CRC therapies., Competing Interests: None., (IJCEP Copyright © 2017.)