miR-532-5p Inhibits Non-Small Cell Lung Cancer Progression In Vivo and In Vitro by Targeting Yin Yang 1.

Lung cancer is a common cancer that is familiar to people and has the highest global incidence; among all lung cancer patients, 85% are non-small cell lung cancer (NSCLC). A number of microRNAs (miRNAs), including miR-532-5p, are implicated in the pathophysiological processes of tumorigenesis. However, the mechanism of miR-532-5p in NSCLC remains unclear. In the current study, the expression of miR-532-5p was found to be markedly downregulated in clinical NSCLC tissues and cell lines. Further study indicated that ectopic expression of miR-532-5p inhibited NSCLC cell proliferation and invasion while accelerating in vitro, but silencing miR-532-5p had an opposite result. Furthermore, functional experiments revealed that miR-532-5p effectively blocked tumor growth in a xenograft tumor mouse model. Bioinformatics and luciferase reporter analysis verified that Yin Yang 1 (YY1) transcripts are targets of miR-532-5p. Moreover, the expression of YY1 was negatively regulated by miR-532-5p in NSCLC cells. In vivo assays indicated that downregulation of YY1 inhibited tumor growth. Notably, overexpression of YY1 effectively counteracted the tumor-suppressing effects of miR-532-5p in vitro and in vivo. In summary, this study demonstrated the tumor-suppressive role of miR-532-5p in NSCLC by regulating YY1 in vitro and in vivo.

MicroRNA-221-3p alleviates cell apoptosis and inflammatory response by targeting cyclin dependent kinase inhibitor 1B in chronic obstructive pulmonary disease.

As a chronic bronchitis or emphysema featured by airflow obstruction, chronic obstructive pulmonary disease (COPD) can further develop into respiratory failure and pulmonary heart diseases. MicroRNAs (miRNAs) are crucial mediators in COPD. Nevertheless, the specific role and molecular mechanism of microRNA-221-3p (miR-221-3p) in COPD are unclear. This research aimed to probe into the role of miR-221-3p in COPD. Bioinformatics analysis and a series of assays including western blot, luciferase reporter, reverse transcription quantitative polymerase chain reaction, flow cytometry, cell counting kit-8 and enzyme linked immunosorbent assay were used to explore the functions and mechanism of miR-221-3p in COPD. First, miR-221-3p level was validated to be lowly expressed in the lung tissues of COPD patients and 16HBE cells stimulated by cigarette smoke extract (CSE). Functionally, miR-221-3p overexpression inhibited inflammatory response and apoptosis in CSE-treated 16HBE cells. Moreover, we predicted 5 potential targets of miR-221-3p and found that miR-221-3p shared binding site with cyclin dependent kinase inhibitor 1B (CDKN1B). CDKN1B was targeted by miR-221-3p in CSE-treated 16HBE cells. CDKN1B was negatively modulated by miR-221-3p. Finally, rescue experiments demonstrated that overexpressed CDKN1B counteracted the influences of miR-221-3p on apoptosis and inflammatory response in CSE-treated 16HBE cells. Our data showed that miR-221-3p alleviated cell apoptosis and inflammatory response via targeting CDKN1B in an in vitro model of COPD.

Damage to the nigrostriatal system in the MPTP-treated SAMP8 mouse.

Application of aged animals to studies of Parkinson's disease (PD) will be beneficial to improve the understanding of its pathogenesis. The senescence-accelerated mouse prone8 (SAMP8) mouse has an early onset of senility and a short life span, characterized by learning and memory impairment, and affective disturbance in the aging process. There is no animal currently being used as a PD model that exhibits these characteristics. Application of the SAMP8 mouse to PD research may have several merits. For the first time, we have investigated damage of the nigrostriatal system in the SAMP8 mouse induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Male SAMP8 mice (12 weeks) were treated with four subcutaneous injections of MPTP (20mg/kg at 2h intervals): spontaneous activity decreased significantly after the third injection, and recovered 48h after the first injection. In MPTP-SAMP8 mice, the tyrosine hydroxylase (TH)-positive neuronal loss at 6h (7.06%), 24h (12.79%), 3 days (22.49%), and 8 days (42.39%), while striatal dopamine (DA) levels decreased at 6h by 79.09%, at 24h by 80.33%, at 3 days by 83.86%, and at 8 days by 80.14%. These results indicated that there were marked decreases in striatal DA levels and a loss of dopaminergic neurons in the substantia nigra, with the behavior change following shortly thereafter, in MPTP-SAMP8 mice. On the basis of the current findings, the SAMP8 mouse is also vulnerable to neurotoxic effects of MPTP. These data suggest that the SAMP8 mouse may be utilized in PD research.