GLIDR promotes the aggressiveness progression of prostate cancer cells by sponging miR-128-3p.

Glioblastoma downregulated RNA (GLIDR) is a newly discovered long non-coding RNA (lncRNA) that its increased expression indicates a poor prognosis of prostate cancer (PCa). However, the effect of GLIDR on PCa cells is not clear. Our study investigated the role and molecular mechanism of GLIDR in PCa cells. The results showed that GLIDR expression levels were higher in PCa samples and cells than in control. GLIDR could regulate the invasive potential, epithelial-to-mesenchymal transition (EMT) and proliferation in PC-3 and LnCaP cells. Besides, GLIDR could weaken the inhibitory effects of miR-128-3p on invasion, EMT and proliferation in PCa cells. Western blotting proved that miR-128-3p affected the expression of EMT markers, such as E-cadherin, Snail and N-cadherin, and GLIDR could reversed the effects of miR-128-3p on the expression levels of EMT markers in PCa cells. In addition, knockdown of miR-128-3p stimulated the invasion, EMT, and proliferation in PCa cells, whereas these effects were reversed when GLIDR expression was knocked down. GLIDR knockdown inhibited the invasion, EMT, and proliferation in PCa cells, and GLIDR was shown to sponge miR-128-3p. Together, these results highlight GLIDR as a potential therapeutic target for the PCa treatment.

Safety and efficacy profile of cyclin-dependent kinases 4/6 inhibitor palbociclib in cancer therapy: A meta-analysis of clinical trials.

BACKGROUND: Palbociclib is a small-molecule, cyclin-dependent kinase 4 and 6 inhibitor, which prevents phosphorylation of the retinoblastoma (Rb) protein and inhibits cell-cycle progression from G1 to S phase. We performed this meta-analysis to estimate the safety and efficacy of palbociclib in cancer patients from clinical trials. METHODS: PubMed and EMBASE were searched for eligible studies. Adverse events (AE) of grade ≥3 and all-grade (1-5) were extracted to calculate event rates. Odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the safety of palbociclib in endocrine treatment-combined studies. A fixed effects model was used when homogeneity was low (I2  ≤ 50%). A random effects model was adopted when there was a significant heterogeneity (I2  > 50%). For efficacy endpoints, hazard ratio (HR) and 95% CI for progression-free survival (PFS) or overall survival (OS) were extracted and analyzed. RESULTS: Nine clinical trials representing 1534 patients were identified. The most frequently observed all-grade adverse events (AEs) in patients treated with palbociclib were neutropenia (event rate: 68.1%), leukopenia (51.7%), fatigue (35.9%), anemia (34.7%), and thrombocytopenia (30.9%). The most common grade 3 or more toxicities were neutropenia (51.6%), leukopenia (29.4%), and thrombocytopenia (7.5%). Hematologic adverse events had high occurrence in the palbociclib group. The pooled analysis of survival outcomes suggested that palbociclib produced clinical benefits in breast cancers and Rb-positive tumors. More specifically, palbociclib was associated with significant improvement of PFS (HR: 0.518, 95% CI: 0.444-0.604) in the treatment of ER-positive and HER2-negative breast cancer. CONCLUSIONS: Hematologic adverse events were common in palbociclib-treated cancer patients. Since palbociclib produced a higher PFS rate with a low serious complication rate, it can be a promising novel target therapy drug for treating ER-positive and HER2-negative breast cancer.

Associations of single nucleotide polymorphisms in miR-146a, miR-196a, miR-149 and miR-499 with colorectal cancer susceptibility.

BACKGROUND: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-196a2*T variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. CONCLUSIONS: These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.

Elastography for the differentiation of benign and malignant liver lesions: a meta-analysis.

The objective of this paper was to evaluate the overall accuracy of elastography in the diagnosis of benign and malignant liver lesions by liver biopsy as the gold standard. Literature databases were searched. The studies which were related to evaluate the diagnostic value of elastography for differentiation in benign and malignant liver lesions in English or Chinese were included. The summary receiver operating characteristic (SROC) curve was performed, and the areas under the curve (AUC) were also calculated to present the accuracy of the elastography for the diagnosis of benign and malignant liver lesions. Six studies which included a total of 448 liver lesions in 384 patients were analyzed. The summary sensitivity and specificity of elastography for the differentiation of malignant liver lesions were 85% (95% CI, 80 to 89%) and 84% (95% CI, 80 to 88%), respectively. And the summary diagnostic odds ratio was 46.33 (95% CI, 15.22 to 141.02), and the SROC was 0.9328. Elastography has a high sensitivity and specificity differentiation for benign and malignant liver lesions. As a non-invasive method, it is promising to be applied to clinical practice. To estimate elastography objectively, a large, prospective, international, and multi-center study is still needed.

Association between rs11614913 polymorphism in miR-196a2 and colorectal cancer risk: a meta-analysis.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs of 20-22 nucleotides in length, which regulate the translation or degradation of human messenger RNA (mRNA). MiRNAs involve in the regulation of most biological processes, as well as human diverse diseases including cancer. Recently, many studies investigated the association between miR-196a2 rs11614913 polymorphism and colorectal cancer (CRC), which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 6 studies that included 1800 cases and 2329 controls. There was a statistically decreased risk of CRC in dominant model, recessive model and homozygous model. In the Asian group, significantly decreased susceptibility of CRC was found in allele model, dominant model, recessive model and homozygous model. As for the Caucasian group, none of genetic models demonstrates significant association between miR-196a2 rs11614913 polymorphism and susceptibility of CRC. CONCLUSIONS: These findings supported that miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of CRC.