Long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) has been implicated as a tumor suppressor gene in several human cancer types. However, little is known regarding its involvement and potential mechanism in human breast cancer. In this study, we explored the effect of MEG3 on the growth of human breast cancer cell line MDA‐MB‐231 in vitro and in vivo, and sought to elucidate the potential signaling mechanisms. Ectopic overexpression of MEG3 using a lentiviral vector Lv‐MEG3 significantly inhibited breast cancer cell growth in vitro and a cancer xenograft growth in vivo. MEG3 overexpression led to marked increase of apoptosis in breast cancer cells as determined using flow cytometry and fragmented DNA labeling. Moreover, ectopic expression of MEG3 increased the expression of endoplasmic reticulum (ER) stress–related proteins required for unfolded protein response, including glucose‐regulated protein 78 (GRP78), inositol‐requiring enzyme 1 (IRE1), protein kinase RNA (PKR)‐like ER kinase (PERK), and activated transcription factor 6 (ATF6), as well as proapoptotic proteins CCAAT/enhancer binding protein homologous protein (CHOP) and caspase‐3. Finally, MEG3 overexpression markedly increased nuclear factor κB (NF‐κB) expression, NF‐κB translocation to the nucleus, and p53 expression, whereas pharmacological inhibition of NF‐κB completely abolished MEG3‐induced activation of p53. Together, these results suggest that MEG3 inhibits breast cancer growth and induces breast cancer apoptosis, partially via the activation of the ER stress, NF‐κB and p53 pathways, and that NF‐κB signaling is required for MEG3‐induced p53 activation in breast cancer cells. Our results indicate targeting lncRNA MEG3 may represent a novel strategy for breast cancer therapy.

No abstract

The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This study aimed to conduct a meta-analysis and literature review and investigate clinicopathological significance of CHFR promoter hypermethylation in CRC. The following online database were used: PubMed, EMBASE, and Web of Science up to March 2017. Odds Ratios (OR) and Hazard Ratios (HR) with 95% corresponding confidence intervals (CIs) were calculated. A total of seven relevant articles were available for meta-analysis which included 966 patients. The frequency of CHFR promoter hypermethylation significantly increased in CRC compared to normal colorectal mucosa tissue, pooled OR was 8.35, p < 0.00001. CHFR promoter hypermethylation was not significantly correlated to stage, OR was 1.16, p = 0.63. However, CHFR promoter hypermethylation was more frequently observed in CRC with positive lymph nodes metastasis than CRC with negative lymph nodes metastasis, OR was 0.46, p = 0.03. Additionally CHFR promoter hypermethylation was significantly related to poor overall survival in patients with CRC, HR was 0.62, p = 0.008. Based on these results, tumor CHFR promoter hypermethylation is not only a diagnostic biomarker for CRC, but also a prognostic marker. CHFR promoter hypermethylation is significantly associated with worse overall survival in patients with CRC. Our data suggested that CHFR could be a potential drug target for development of demethylation treatment for patients with CRC.

ABSTRACT. IL-16 plays an important role in affect the secretion of tumor-related inflammatory cytokines. We aimed to assess the role of interleukin-16 (IL-16) rs4778889 T/C and rs11556218 T/G polymorphisms in the occurrence of renal cell cancer (RCC). This study is composed of 274 RCC patients and 274 control subjects. Genotyping of polymorphisms was performed using polymerase chain reaction combined with restriction fragment length polymorphism analysis. All statistical analysis was carried out by the SPSS statistical software package, version 16.0 (SPSS Inc., Chicago, IL, USA). Using conditional logistic regression analysis, the TC and CC genotypes of rs4778889 exhibited a higher risk of RCC, with adjusted ORs (and 95%CIs) of 1.79 (1.23-2.62) and 2.67 (1.29-5.69), respectively. Moreover, under dominant and recessive models, individuals carried the rs4778889 polymorphism was exhibited elevated RCC risk, with adjusted ORs (and 95%CI) of 1.93 (1.35-2.76) and 2.11 (1.05-4.45), respectively. No significant differences were observed in rs11556218 genotype frequencies between the study groups. In conclusion, the results of our study reveal an association between the IL-16 rs4778889 polymorphism and heightened risk of RCC.

Background Taurine-upregulated gene 1 ( TUG1 ) has been documented to be implicated in carcinogenesis and chemoresistance in solid tumors. Here, we explored the biological role and regulatory mechanism of TUG1 in progression and chemoresistance of urothelial carcinoma of the bladder (UCB). Methods Nuclear factor-erythroid 2 ( NF-E2 ) -related factor 2 ( Nrf2 ) mRNA and TUG1 expression was determined by quantitative reverse transcription polymerase chain reaction. Western blot was performed to determine the protein levels of Nrf2, p-glycoprotein (p-gp), Ki-67 (Ki67), matrix metalloproteinase (MMP)-2 and MMP-9 and cleaved caspase-3. The effects of either Nrf2 or TUG1 knockdown on the proliferation, invasion, apoptosis and adriamycin (ADM) resistance of UCB cells were evaluated by CCK-8 assay, transwell invasion assay and flow cytometry analysis. Xenograft tumor assay was carried out to confirm the role of Nrf2 and TUG1 in ADM resistance of UCB cells in vivo. Results Nrf2 and TUG1 were upregulated in UCB tissues and cell lines. A positive correlation between Nrf2 and TUG1 expression was discovered in UCB tissues. Moreover, Nrf2 and TUG1 expression levels were higher in ADM-resistant cells compared with those in parental cells. Furthermore, Nrf2 positively regulated the expression of TUG1 in UCB cells. Knockdown of either Nrf2 or TUG1 led to the inhibition of cell proliferation and invasion and promotion of cell apoptosis, accompanying with down-regulation of Ki67, MMP-2 and MMP-9 and up-regulation of cleaved caspase-3. Knockdown of either Nrf2 or TUG1 enhanced the sensitivity of BIU-87/ADM and T24/ADM cells to ADM, as indicated by decreased expression of p-gp. Besides, knockdown of either Nrf2 or TUG1 inhibited tumor growth in the absence or presence of ADM in vivo. Conclusions Nrf2 induces the up-regulation of TUG1 to promote progression and ADM resistance in UCB.