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Wnt signaling plays an important role in regulating the biological behavior of cancers, and many drugs targeting this signaling have been developed. Recently, a series of research have revealed that Wnt signaling could regulate DNA damage response (DDR) which is crucial for maintaining the genomic integrity in cells and closely related to cancer genome instability. Many drugs have been developed to target DNA damage response in cancers. Notably, different components of the Wnt and DDR pathways are involved in crosstalk, forming a complex regulatory network and providing new opportunities for cancer therapy. Here, we provide a brief overview of Wnt signaling and DDR in the field of cancer research and review the interactions between these two pathways. Finally, we also discuss the possibility of therapeutic agents targeting Wnt and DDR as potential cancer treatment strategies.

BackgroundNasopharyngeal cancer (NPC) has a high incidence in Southern China and Asia, and its survival is extremely poor in advanced patients. MiRNAs play critical roles in regulating gene expression and serve as therapeutic targets in cancer. This study sought to disclose key miRNAs and target genes responsible for NPC prognosis and endocrine metabolism.Materials and methodsThree datasets (GSE32960, GSE70970, and GSE102349) of NPC samples came from Gene Expression Omnibus (GEO). Limma and WGCNA were applied to identify key prognostic miRNAs. There were 12 types of miRNA tools implemented to study potential target genes (mRNAs) of miRNAs. Univariate Cox regression and stepAIC were introduced to construct risk models. Pearson analysis was conducted to analyze the correlation between endocrine metabolism and RiskScore. Single-sample gene set enrichment analysis (ssGSEA), MCP-counter, and ESTIMATE were performed for immune analysis. The response to immunotherapy was predicted by TIDE and SubMap analyses.ResultsTwo key miRNAs (miR-142-3p and miR-93) were closely involved in NPC prognosis. The expression of the two miRNAs was dysregulated in NPC cell lines. A total of 125 potential target genes of the key miRNAs were screened, and they were enriched in autophagy and mitophagy pathways. Five target genes (E2F1, KCNJ8, SUCO, HECTD1, and KIF23) were identified to construct a prognostic model, which was used to divide patients into high group and low group. RiskScore was negatively correlated with most endocrine-related genes and pathways. The low-risk group manifested higher immune infiltration, anticancer response, more activated immune-related pathways, and higher response to immunotherapy than the high-risk group.ConclusionsThis study revealed two key miRNAs that were highly contributable to NPC prognosis. We delineated the specific links between key miRNAs and prognostic mRNAs with miRNA–mRNA networks. The effectiveness of the five-gene model in predicting NPC prognosis as well as endocrine metabolism provided a guidance for personalized immunotherapy in NPC patients.

Abstract Background Nasopharyngeal carcinoma (NPC) is a common malignant tumor. Ten-eleven translocation (TET) protein 2 (TET2), an evolutionarily conserved dioxygenases, is reported to be involved in various malignant tumor developments. Here, we aim to investigate the effect of TET2 on NPC progress in vitro and in vivo, and its detailed underlying mechanism. Methods Real-time PCR and western blotting were used to determine the expression levels of TET1/2/3 in NPC cell lines. The effects of TET2 on NPC progression were evaluated using CCK8 and invasion assays in vitro. Proteins interacted with TET2 in NPC cells were detected by immunoprecipitation and mass spectrometry. The effects of TET2 or pyruvate kinase, muscle (PKM) on glycolysis in NPC cells were examined by detecting glucose uptake and lactate production. The effects of TET2 on NPC progression were evaluated using xenograft tumor model in vivo. Results TET2 expression was decreased in NPC cells, and TET2 overexpression inhibited proliferation and invasion of NPC cells, which is independent on TET2’s catalytic activity. In mechanism, TET2 N-terminal domain interacts with PKM in cytoplasm to prevent PKM dimers from translocating into nucleus, suppressing glycolysis in NPC cells, thereby inhibiting proliferation and invasion of NPC cells. Moreover, using xenograft tumor model, we found that TET2 knockout promoted NPC progression and decreased survival rate. However, administration with the inhibitor of PKM, shikonin, decreased the tumor volume of TET2-cas9 group, and increased the survival rate. Conclusion TET2 suppresses NPC development through interacting with PKM to inhibit glycolysis.

Abstract Background Hepatocellular carcinoma (HCC) is still the most common cause of cancer-related mortality worldwide and accumulating studies report that HCC is frequently linked to chronic inflammation. G-protein alpha-subunit (GNAS)-activating mutations have recently been reported to form a rare subgroup of inflammatory liver tumors. In this study, we investigated the roles of GNAS in inflammation-related HCC progression and its underlying mechanism. Methods Lipopolysaccharides (LPS) and diethylnitrosamine were employed to stimulate HCC cells to an induced inflammatory response. qRT-PCR, immunohistochemistry and immunoblotting were performed to detect the expression of GNAS in HCC tissues and cell lines. Expression levels of proinflammatory cytokines were detected by qRT-PCR and ELISA. N6-methyladenosine (m6A) methylation of GNAS mRNA was detected by RNA-binding protein immunoprecipitation (RIP). Transcription factors activation profiling plate array was performed to investigate the underlying mechanism in GNAS promoting interleukin-6 (IL-6) expression in HCC cells. HCC cell invasion was determined by transwell assay in vitro, and tumorigenesis was assessed with a subcutaneous xenograft mouse model of HCC. Results We found that LPS stimulation promotes GNAS expression in HCC cells through increasing m6A methylation of GNAS mRNA. The high expression level of GNAS promotes LPS-induced HCC cell growth and invasion by interacting with signal transducer and activator of transcription 3 (STAT3). Furthermore, GNAS knockdown inhibits LPS induced-IL-6 expression in HCC cells by suppressing STAT3 activation. Moreover, we found that GNAS promotes LPS-induced STAT3 activation in HCC cells through inhibiting long non-coding RNA TPTEP1 interacting with STAT3. In addition, GNAS expression promotes HCC development in mice and is related to poor survival. Conclusions Our findings for the first time indicate a tumor-promoting role of GNAS in inflammation-related HCC progression and provide a novel potential target for HCC therapy.

Head and neck cancers (HNCs) rank as the sixth common and the seventh leading cause of cancer-related death worldwide, with an estimated incidence of 600,000 cases and 40–50% mortality rate every year. Radiotherapy is a common local therapeutic modality for HNC mainly through the function of ionizing radiation, with approximately 60% of patients treated with radiotherapy or chemoradiotherapy. Although radiotherapy is more advanced and widely used in clinical practice, the 5-year overall survival rates of locally advanced HNCs are still less than 40%. HNC cell resistance to radiotherapy remains one of the major challenges to improve the overall survival in HNC patients. Non-coding RNAs (ncRNAs) are newly discovered functional small RNA molecules that are different from messenger RNAs, which can be translated into a protein. Many previous studies have reported the dysregulation and function of ncRNAs in HNC. Importantly, researchers reported that several ncRNAs were also dysregulated in radiotherapy-sensitive or radiotherapy-resistant HNC tissues compared with the normal cancer tissues. They found that ectopically elevating or knocking down expression of some ncRNAs could significantly influence the response of HNC cancer cells to radiotherapy, indicating that ncRNAs could regulate the sensitivity of cancer cells to radiotherapy. The implying mechanism for ncRNAs in regulating radiotherapy sensitivity may be due to its roles on affecting DNA damage sensation, inducing cell cycle arrest, regulating DNA damage repair, modulating cell apoptosis, etc. Additionally, clinical studies reported that in situ ncRNA expression in HNC tissues may predict the response of radiotherapy, and circulating ncRNA from body liquid serves as minimally invasive therapy-responsive and prognostic biomarkers in HNC. In this review, we aimed to summarize the current function and mechanism of ncRNAs in regulating the sensitivity of HNC cancer cells to radiotherapy and comprehensively described the state of the art on the role of ncRNAs in the prognosis prediction, therapy monitoring, and prediction of response to radiotherapy in HNC.

Nasopharyngeal carcinoma (NPC) is the most common type of malignancy of the neck and head in Southeast Asia and North Africa. Long noncoding RNA (LncRNA) Differentiation antagonizing nonprotein coding RNA (DANCR) has been reported to exert oncogenic functions in various malignant tumors. However, whether DANCR is involved in NPC tumorgenesis and its underlying mechanisms are still unknown. In the current study, we investigated the expression and biological functions of DANCR in NPC cells and found that DANCR is highly expressed in NPC cells and IL-6 stimulation upregulates DANCR expression through an STAT3-dependent manner. Besides, DANCR knockdown attenuates IL-6-induced proliferation and invasion of NPC cells. Furthermore, DANCR specifically interacts with STAT3 to promote STAT3 activation in NPC cells. Moreover, DANCR knockdown evidently decreases IL-6 induced the association between STAT3 and JAK1 in NPC cells. In addition, we also found that DANCR also indirectly binds to JAK1 through interacting with STAT3 under IL-6 stimulation in NPC cells. Taken together, the present study for the first time demonstrates that DANCR, acting as an oncogene in NPC, promotes NPC progression by interacting with STAT3 and enhancing JAK1 binding to STAT3 to strengthen IL-6/JAK1/STAT3 signaling, suggesting that it may be a potential target to be used as a novel strategy to develop NPC therapeutics.

The material characteristics and properties of transition metal dichalcogenide (TMDCs) have gained research interest in various fields, such as electronics, catalytic, and energy storage. In particular, many researchers have been focusing on the applications of TMDCs in dealing with environmental pollution. TMDCs provide a unique opportunity to develop higher-value applications related to environmental matters. This work highlights the applications of TMDCs contributing to pollution reduction in (i) gas sensing technology, (ii) gas adsorption and removal, (iii) wastewater treatment, (iv) fuel cleaning, and (v) carbon dioxide valorization and conversion. Overall, the applications of TMDCs have successfully demonstrated the advantages of contributing to environmental conversation due to their special properties. The challenges and bottlenecks of implementing TMDCs in the actual industry are also highlighted. More efforts need to be devoted to overcoming the hurdles to maximize the potential of TMDCs implementation in the industry.