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Cardiac hypertrophy is an adaptive cardiac response that accommodates the variable hemodynamic demands of the human body during extended periods of preload or afterload increase. In recent years, an increasing number of studies have pointed to a potential connection between myocardial hypertrophy and abnormal expression of non-coding RNAs. Circular RNA (circRNA), as one of the non-coding RNAs, plays an essential role in cardiac hypertrophy. However, few studies have systematically analyzed circRNA-related competing endogenous RNA (ceRNA) regulatory networks associated with cardiac hypertrophy. Therefore, we used public databases from online prediction websites to predict and screen differentially expressed mRNAs and miRNAs and ultimately obtained circRNAs related to cardiac hypertrophy. Based on this result, we went on to establish a circRNAs-related ceRNA regulatory network. This study is the first to establish a circRNA-mediated ceRNA regulatory network associated with myocardial hypertrophy. To verify the results of our analysis, we used PCR to verify the differentially expressed mRNAs and miRNAs in animal myocardial hypertrophy model samples. Our findings suggest that three mRNAs (Col12a1, Thbs1, and Tgfbr3), four miRNAs (miR-20a-5p, miR-27b-3p, miR-342-3p, and miR-378a-3p), and four related circRNAs (circ_0002702, circ_0110609, circ_0013751, and circ_0047959) may play a key role in cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate interactions between miR-214, PTEN, and WWOX and their effect on AKT signaling during the NPC progression. Nasopharyngeal carcinoma (NPC) was highly prevalent with poor prognosis among the patients. MiR-214 reported as an important NPC biomarker was associated with regulation of biological functions. Methods: 5-8F and 6-10B NPC cells were transfected with miR-214 inhibitor. MTT and colony formation assays were performed to assess cell proliferation. PI staining assay was performed to determine distribution of cell cycle. Annexin-V/PI staining assay was used to evaluate cell apoptosis in NPC. The effects of miR-214 inhibitor on the expression levels of PTEN, WWOX, AKT signaling pathway, cell-cycle-, and apoptosis-associated proteins were assessed by Western blotting or qRT-PCR assay. PTEN and WWOX were knocked down using the corresponding shRNA to investigate their effects on miR-214 inhibitor involved in proapoptosis and antiproliferation mechanisms in NPC. Results: Inhibition of miR-214 suppressed cell growth and induced apoptosis of 5-8F and 6-10B cells. MiR-214 regulated the expression of both PTEN and WWOX through targeting the 3'-UTR. Inhibition of miR-214 promoted WWOX and PTEN expression, inactivated AKT signaling pathway, and regulated cell-cycle- and apoptosis-associated proteins. Knockdown of PTEN or WWOX reversed effects of miR-214 inhibitor on AKT signaling, cell proliferation, and apoptosis. Conclusion: MiR-214 was suggested to induce cell proliferation and inhibit cell apoptosis of NPC through directly targeting both PTEN and WWOX, which provided a novel therapeutic target for clinical treatment of NPC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a common malignant tumor and long non-coding RNAs (lncRNAs) are widely involved in NPC development. Nevertheless, the role of lncRNA FAM225A in NPC remain unclear. Here, we evaluated the effect of FAM225A on NPC cell proliferation, migration and epithelial-mesenchymal transition (EMT). Levels of FAM225A and CENP-N in NPC tissues and cells were measured using RT-qPCR. Western blot assessed CENP-N, Snail, E-cadherin, N-cadherin, Vimentin, cGAS and p-STING levels. FAM225A expression was knocked down by sh-FAM225A or overexpressed by pcDNA-FAM225A. RIP and RNA pull-down verified the binding between FAM225A, CENP-N and FUS. Cell proliferation, migration and invasion were evaluated by CCK8, colony formation and transwell assays. FAM225A and CENP-N expression levels were evaluated in NPC tissues and cell lines. FAM225A knockdown inhibited NPC cell proliferation, migration and EMT. FAM225A stabilized CENP-N mRNA by recruiting FUS. FAM225A activated cGAS-STING by regulating the expression of CENP-N to promote NPC cell proliferation, migration and EMT. FAM225A regulates NPC progression via FUS/CENP-N mediated cGAS-STING signaling pathway, which provides new therapeutic targets for developing new NPC treatments. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: RNA interference (RNAi) is an evolutionary conserved mechanism for specific gene silencing. There are currently numerous cancer therapy clinical trials based on RNAi technology. Using an adenoviral system as a delivery mediator of RNAi, we investigated the therapeutic effects of targeting three genes simultaneously in vitro and in vivo. In this study, we constructed an recombinant adenoviral shRNA expression system as Adv-pEGFP-shVEGF-shTERT-shBcl-xl for multi-genes silencing. Our results showed that the adenoviral vector can achieve above 90% of transfection efficiency and induced obvious apoptosis in CNE-2 cell both in vitro and in vivo compared with targeting the TERT alone or controlled group. [Copyright &y& Elsevier]

Abstract The present study aimed to investigate the effects and mechanisms of PLAC8 on the epithelial-mesenchymal transition (EMT) of Nasopharyngeal carcinoma (NPC). The expression of PLAC8 in NPC and nasopharyngitis (NPG) tissues from 150 patients was determined using immunohistochemistry. The levels of PLAC8 in five NPC cell lines and nasopharyngeal permanent epithelial cell line were measured using western blotting. We then knocked out or overexpressed PLAC8 in CNE2 cells. Cell proliferation, wound healing, migration, and invasion assays were used to analyze the effects of PLAC8 on the proliferation, migration, and invasion in vivo and vitro. The results showed that the expression of PLAC8 was much higher in NPC tissues than in NPG tissues. The expression of PLAC8 was higher in all the cell lines than in the nasopharyngeal permanent epithelial cells. PLAC8 knockout resulted in significant decreases in cell proliferation, migration, and invasion; associated with lower protein levels of N-cadherin; and increased levels of E-cadherin. Overexpression of PLAC8 had the opposite effect. Furthermore, knockout of PLAC8 inactivated TGF-β/SMAD signaling pathway and suppressed the growth of NPC xenografts. PLAC8 may promote the carcinogenesis and EMT of NPC via the TGF-β/Smad pathway, which suggests that PLAC8 may be a potential biomarker for NPC. Highlights • PLAC8 is up-regulated in Nasopharyngeal Carcinoma, and can promote Nasopharyngeal Carcinoma cell migration and invasion. • PLAC8 can enhance the process of EMT in Nasopharyngeal Carcinoma. • PLAC8 might induce EMT through TGF-β/Smad signaling pathway in Nasopharyngeal Carcinoma. [ABSTRACT FROM AUTHOR]