Background and ObjectiveYes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are nuclear effectors of the Hippo pathway. Although they are abundantly expressed in the cytoplasm and nuclei of human colorectal cancer (CRC), and related to tumor proliferation status, there have been few studies on the predictive role of YAP and TAZ expression on the overall survival of patients with CRC. This study investigated YAP and TAZ expression in both CRC patients and colon cancer cell lines, and assessed their prognostic value.MethodsParaffin-embedded specimens from 168 eligible patients were used to investigate YAP and TAZ expression by immunohistochemistry, and compared with experimental results in colon cancer HCT116 cell line to explore their clinical significance in CRC.ResultsStatistically significant positive correlations were found between protein expression of YAP and TAZ in CRC tissues. Patients with higher YAP or TAZ expression showed a trend of shorter survival times; more importantly, our cohort study indicated that patients with both YAP and TAZ overexpression presented the worst outcomes. This was supported by multivariate analysis. In HCT116 colon cancer cells, the capacity for proliferation, metastasis, and invasion was dramatically reduced by knockdown of YAP and TAZ expressions by siRNA.ConclusionsCo-overexpression of YAP and TAZ is an independent predictor of prognosis for patients with CRC, and may account for the higher proliferation, metastasis, and poor survival outcome of these patients.

N6-methyladenosine (m6A) is a reversible mRNA modification that has been shown to play important roles in various biological processes. However, the roles of m6A modification in macrophages are still unknown. Here, we discover that ablation of Mettl3 in myeloid cells promotes tumour growth and metastasis in vivo. In contrast to wild-type mice, Mettl3-deficient mice show increased M1/M2-like tumour-associated macrophage and regulatory T cell infiltration into tumours. m6A sequencing reveals that loss of METTL3 impairs the YTHDF1-mediated translation of SPRED2, which enhances the activation of NF-kB and STAT3 through the ERK pathway, leading to increased tumour growth and metastasis. Furthermore, the therapeutic efficacy of PD-1 checkpoint blockade is attenuated in Mettl3-deficient mice, identifying METTL3 as a potential therapeutic target for tumour immunotherapy.

BackgroundPrevious work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2.Methodology/PrincipalFindings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3′UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo.Conclusions/SignificanceThese findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer.

Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are widely expressed in eukaryotic cells. In contrast to the generation of linear RNA transcripts, circRNAs undergo a “back-splicing” process to form a continuous, covalently closed, stable loop structure without 5ʹ or 3ʹ polarities and poly (A) tails during posttranscriptional modification. Due to the widespread availability of several technologies, especially high-throughput RNA sequencing, numerous circRNAs have been discovered not only in mammals but also in plants and insects. Notably, due to their abilities to serve as microRNA (miRNA) “sponges”, miRNA “reservoirs”, regulate gene expression and encode proteins, circRNAs participate in the development and progression of different immune responses and immune diseases by enriching various forms of epigenetic modification. CircRNAs have been demonstrated to be expressed in a tissue-specific and pathogenesis-related manner during the occurrence of multiple immune diseases. Additionally, because of their circular configurations, expression in blood and peripheral tissues and coexistence with exosomes, circRNAs show inherent conservation along with environmental resistance stability and may be regarded as potential biomarkers or therapeutic targets for some immune diseases. In this review, we summarize the characteristics, functions and mechanisms of circRNAs and their involvement in immune responses and diseases. Although our knowledge of circRNAs remains preliminary, this field is worthy of deeper exploration and greater research efforts.