MicroRNA-202 induces cell cycle arrest and apoptosis in lung cancer cells through targeting cyclin D1.

OBJECTIVE: MicroRNAs are critical regulators in tumorigenesis. This study is aimed at investigating the function of miR-202 in the proliferation of human lung cancer cells. PATIENTS AND METHODS: Lung cancer tissues and paired adjacent normal tissues were collected from 20 patients; the expression of miR-202 was tested by Realtime PCR; cell proliferation and cell cycle distribution were determined by CCK-8 assay and flow cytometry, respectively; apoptosis was determined by TUNEL assay and Western blot analysis of cleaved-PARP; the relationship between miR-202 and cyclin D1 mRNA 3'UTR was determined by luciferase activity assay. RESULTS: MiR-202 was significantly reduced in lung cancer tissues compared with the adjacent normal tissues. Overexpression of miR-202 inhibited cell proliferation and induced a G0/G1 cell cycle arrest and apoptosis. Luciferase activity assay and Western blot analysis together showed that miR-202 can bind to the 3'UTR of cyclin D1 mRNA directly and inhibits cyclin D1 expression at the protein level. In addition, restoration of cyclin D1 expression partially abolished cell cycle arrest and apoptosis induced by miR-202. CONCLUSIONS: MiR-202 is constantly downregulated in lung cancer and functions as a tumor suppressive gene via targeting cyclin D1. Modulating the level of miR-202 may be a novel therapeutic method for lung cancer.

Mitral valve repair: results and the decision-making process in reconstruction. Report of 275 cases.

From January 1975 to June 1988, 275 patients underwent mitral valve repair for mitral regurgitation, pure (148 patients) or associated with mitral stenosis (127 patients). Patients with pure mitral stenosis were excluded from this study. The cause of mitral regurgitation was rheumatic in 180 patients (aged 28.6 +/- 1.2 years, mean +/- standard error of the mean) and degenerative in 84 patients (aged 54.7 +/- 1.5 years). Fifty-nine percent of the patients were in New York Heart Association classes III and IV before the operation. Intraoperative assessment of the mitral valve led us to identify four major mechanisms of mitral regurgitation: (1) restriction of leaflet motion by fibrosis (group I, 63 patients); (2) enhancement of leaflet motion by leaflet and chordal extension and prolapse (group II, 139 patients), (3) combination of both (group III, 64 patients); and (4) isolated dilatation of the anulus (group IV, 10 patients). One hundred sixty-one patients had isolated mitral disease and 114 had associated aortic or tricuspid valve disease, or both. The hospital mortality rate was 4.0%. Follow-up was 96% complete and totaled 1247.47 patient-years. At 13 years' follow-up, the survival rate was 93.0% +/- 6.8% in group I, 90.0% +/- 6.0% in group II, and 96.6% +/- 4.6% in group III. Freedom from reoperation was 78.1% +/- 21.0%, 83.2% +/- 18.9%, and 79.6% +/- 16.2%, respectively. Freedom from embolism was 94.7% for the whole series. In patients with isolated mitral valve repair, the cumulative morbidity was significantly higher in groups I (6.3 +/- 2.0%/pt-yr) and III 6.3% +/- 1.7%/pt-yr) than in group II (2.5% +/- 0.9%/pt-yr, p less than 0.05). Multivariate analysis identified age and associated tricuspid valve disease as significant predictors of reoperation (p less than 0.01 for both factors). These results suggest that conservative surgery should be used with caution in group I and III patients. In contrast, indications for mitral valve repair should be extended in group II patients. This observation has important clinical implications since, in Western countries, valve prolapse tends to be a major cause of mitral regurgitation.