These findings reveal the mechanism of X-chromosome lncRNA JPX and its core regulatory circuitry JPX/miR-145-5p/CCND2 in the development and progression of NSCLC, which bring us closer to an understanding of the molecular drivers of NSCLC cancer.
In tumor subgroup, CCND2 was associated with shorter OS in patients with gastric cancer (HR = 2.20, 95% CI: 1.66-2.92), whereas it might be a tumor suppressor in NSCLC (HR = 0.28, 95% CI: 0.12-0.64).
Furthermore, rescue experiments demonstrated that the restoration of CCND2 may significantly reverse the suppressive roles of miR‑671‑3p overexpression on NSCLC cell proliferation and invasion.
Furthermore, siRNA-mediated downregulation of CCND1 or CCND2 yielded the same effects on proliferation and cell cycle arrest as miR-146a-5p upregulation did in the NSCLC cell lines.
Cyclin D2 was expressed in normal lung tissue, and its expression was reduced in 170 (27%) of 626 NSCLCs with a median duration of follow-up of 64 months.
We observed that aberrant methylation of cyclin D2 was present in 32 of 56 (57%) SCLC cell lines, 7 of 32 (22%) SCLC tumor tissues; 25 of 61 (47%) NSCLC cell lines, 19 of 48 (40%) NSCLC tumor tissues; 18 of 30 (60%) breast tumor cell lines and 19 of 63 (30%) breast tumor tissues.