LNCRNA CDKN2B-AS1 regulates mesangial cell proliferation and extracellular matrix accumulation via miR-424-5p/HMGA2 axis.

BACKGROUND: Previous study has demonstrated that long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) was abnormally expressed in diabetic nephropathy (DN). However, the underlying mechanism that allows CDKN2B-AS1 in the progression of DN remains to be further elucidated. METHODS: Peripheral blood cells of 24 diabetes patients with DN and 20 without DN were collected. Human glomerular mesangial cells (HGMC) were cultured in high glucose or low glucose medium. The expression levels of CDKN2B-AS1, microRNA (miR)-424-5p and high mobility group AT hook 2 (HMGA2) were detected by quantitative real-time polymerase chain reaction or western blot. The target association between miR-424-5p and CDKN2B-AS1 or HMGA2 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Cell proliferation, extracellular matrix (ECM) accumulation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and western blot, respectively. RESULTS: CDKN2B-AS1 expression was up-regulated and miR-424-5p level was down-regulated in peripheral blood of DN patients and high glucose-treated HGMC cells. CDKN2B-AS1 was validated as a sponge of miR-424-5p. Silence of CDKN2B-AS1 repressed proliferation and ECM accumulation by increasing miR-424-5p. HMGA2 was a target of miR-424-5p and miR-424-5p overexpression inhibited proliferation, ECM accumulation and PI3K/AKT pathway by targeting HMGA2. Moreover, knockdown of CDKN2B-AS1 inhibited HMGA2 expression and PI3K/AKT pathway by increasing miR-424-5p. CONCLUSION: Knockdown of CDKN2B-AS1 suppressed proliferation, ECM accumulation and PI3K/AKT signaling by increasing miR-424-5p and decreasing HMGA2 in high glucose-treated HMGC cells.

m6A RNA methylation regulators can contribute to malignant progression and impact the prognosis of bladder cancer.

N6-methyladenosine (m6A) is the most common form of messenger RNA (mRNA) modification. An increasing number of studies have proven that m6A RNA methylation regulators are overexpressed in many cancers and participate in the development of cancer through the dynamic regulation of m6A RNA methylation regulators. However, the prognostic role of m6A RNA methylation regulators in bladder cancer (BC) is poorly understood. In the present study, we downloaded the mRNA expression data from The Cancer Genome Atlas (TCGA) database and the corresponding clinical and prognostic information. The relationship between m6A RNA methylation regulators and clinicopathological variables of BC patients was assessed by the Kolmogorov-Smirnov test. The expression of the m6A RNA methylation regulators was differentially associated with different clinicopathological variables of BC patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was then applied to identify three m6A RNA methylation regulators. The risk signature was constructed as follows: 0.164FTO - (0.081YTHDC1+0.032WTAP). Based on the risk signature, the risk score of each patient was calculated, and the patients were divided into a high-risk group and a low-risk group. The overall survival (OS) rate of the high-risk group was significantly lower than that of the low-risk group. The risk signature was not only an independent prognostic marker for BC patients but also a predictor of clinicopathological variables. In conclusion, m6A RNA methylation regulators can participate in the malignant progression of BC, and a risk signature with three selected m6A RNA methylation regulators may be a promising prognostic biomarker to guide personalized treatment for BC patients.