Methylation-mediated gene silencing is closely related to the occurrence and development of human tumors. The euchromatic histone lysine methyltransferase 2 (EHMT2, also known as G9a) is highly expressed in many tumors and is generally considered to be an oncogene, which is associated with the poor outcome of many tumors. Combined immunotherapy and immune checkpoint blockade therapy also have good efficacy and certain safety. However, there are still many difficulties in the drugs targeting G9a, and the combined effect and safety of G9a with many drugs is still under study. This article aims to summarize the role and mechanism of G9a and its inhibitors in tumors in the past two years, and to understand the application prospect of G9a from the perspective of diagnosis and treatment.
Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk.
Genetic Predisposition to Disease , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Polymorphism, Single Nucleotide , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/genetics , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinases/genetics , Risk Factors , Matrix Metalloproteinase 7/genetics , Matrix Metalloproteinase 1/genetics
Castration-resistant prostate cancer (CRPC) is a fatal disease that evolves from prostate cancer due to drug resistance after long-term androgen deprivation therapy. In this study, we aimed to find novel molecular targets for treating CRPC. Through peptidome, we screened out polypeptides dysregulated in the serum of CRPC patients. According to RT-qPCR analysis and cell viability detection, we chose PDZ and LIM Domain 7 (PDLIM7) as the research object. As demonstrated by loss-of-function assays, silencing of PDLIM7 could suppress CRPC cell proliferation, migration, and angiogenesis. Moreover, PDLIM7 knockdown enhanced the sensitivity of CRPC cells to docetaxel treatment. Subsequently, we found that CBP/p300 increases the H3K27ac level in the PDLIM7 promoter to activate PDLIM7. Mechanism experiments such as IP and western blot revealed that PDLIM7 interacted with YAP1 to induce O-Glycosylation of YAP1 and thus stabilize YAP1 protein. Rescue assays demonstrated that PDLIM7 promoted the malignant processes of CRPC cells through YAP1. Finally, an animal study validated that PDLIM7 aggravated tumor growth. In conclusion, our findings highlighted the oncogenic role of PDLIM7 upregulated by CBP/p300-induced H3K27ac enhancement in CRPC by stabilizing YAP1.
Vasodilator-stimulated phosphoprotein (VASP) is an actin-binding protein that includes three structural domains: Enabled/VASP homolog1 (EVH1), EVH2, and proline-rich (PRR). VASP plays an important role in various cellular behaviors related to cytoskeletal regulation. More importantly, VASP plays a key role in the progression of several malignant tumors and is associated with malignant cell proliferation, invasion, and metastasis. Here, we have summarized current studies on the impact of VASP on the development of several malignant tumors and their mechanisms. This study provides a new theoretical basis for clinical molecular diagnosis and molecular targeted therapy.
Exosomes are small membrane-enclosed vesicles that are released by most living cells and harbor a diverse array of proteins, nucleic acids, and lipid cargos. These exosomes offer valuable biomarkers that may offer insights regarding as a range of physiological and pathological processes, including immune responses, cancer development, pregnancy, and diseases of the central nervous system. With the development of high-throughput technologies, the vital functions of long non-coding RNAs (lncRNAs) have been gradually entered peoples vision and become new research hotspots. Nowadays, lncRNAs can play important roles in cancer progression by combining with miRNAs, activating molecular targets and other ways, and are also related to the diagnosis, treatment and prognosis for cancer, such as prostate cancer. Current review focused on the summary of diagnostic roles and mechanistic functions about exosomal lncRNAs in prostate cancer (AU)
Humans , Exosomes/metabolism , MicroRNAs/metabolism , Prostatic Neoplasms , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics
Exosomes are small membrane-enclosed vesicles that are released by most living cells and harbor a diverse array of proteins, nucleic acids, and lipid cargos. These exosomes offer valuable biomarkers that may offer insights regarding as a range of physiological and pathological processes, including immune responses, cancer development, pregnancy, and diseases of the central nervous system. With the development of high-throughput technologies, the vital functions of long non-coding RNAs (lncRNAs) have been gradually entered people's vision and become new research hotspots. Nowadays, lncRNAs can play important roles in cancer progression by combining with miRNAs, activating molecular targets and other ways, and are also related to the diagnosis, treatment and prognosis for cancer, such as prostate cancer. Current review focused on the summary of diagnostic roles and mechanistic functions about exosomal lncRNAs in prostate cancer.
Exosomes , MicroRNAs , Prostatic Neoplasms , RNA, Long Noncoding , Male , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , MicroRNAs/metabolism , Biomarkers/metabolism , Prognosis , Exosomes/metabolism
Objective: A two-electron reductase known as NQO1 [NAD(P)H quinone oxidoreductase 1] is regarded as an excellent anticancer target. Studies have found that rs1800566 polymorphism of NQO1 is linked to different cancers, but their associations remain controversial. Methods: In the present work, we selected to do a comprehensive meta-analysis to analyze their correlation. We performed searches on PubMed, Embase, Google Scholar, Chinese database, and Web of Science. The results we obtained covered all publications before April 3, 2022. Results: There were 176 case-control studies among them, with 56,173 corresponding controls and 43,736 cancer cases. We determined that the NQO1 rs1800566 polymorphism was not related to the cancer risk by calculating 95% confidence intervals and odds ratios. However, stratified genotyping showed that this polymorphism was protective against hepatocellular carcinoma, renal cell carcinoma, and gastric cancer. In addition, on dividing cancer into six systems, the association with gastrointestinal cancer decreased. In the race-based subgroup, a decreasing trend was observed in Asians, while an increasing trend was found among Caucasians, Africans, and mixed populations. The decreased correlation in the hospital-based subgroup was also detected. Conclusion: Current study shows that rs1800566 polymorphism of NQO1 was linked to cancer susceptibility and maybe as a tumor marker in their development.
To shield increasingly severe radiation pollution, ultrathin MXene-based electromagnetic interference (EMI) shielding materials with excellent mechanical properties are urgently demanded in wearable electrical devices or aerospace fields. However, it is still a challenge to fabricate ultrastrong and stiff MXene-based nanocomposites with excellent EMI shielding capacity in a universal and scalable manner. Here, inspired by the natural nacre structure, we propose an efficient superspreading strategy to construct a highly oriented layered "brick-and-mortar" structure using shear-flow-induced alignment of MXene nanosheets at an immiscible hydrogel/oil interface. A continuous and large-area MXene nanocomposite film has been fabricated through a homemade industrial-scale continuous fabrication setup. The prepared MXene nanocomposite films exhibit a tensile strength of 647.6 ± 56 MPa and a Young's modulus of 59.8 ± 6.1 GPa, respectively. These outstanding mechanical properties are attributed to the continuous interphase layer that formed between the well-aligned MXene nanosheets. Moreover, the obtained MXene nanocomposites also show great EMI shielding effectiveness (51.6 dB). We consider that our MXene-based nanocomposite films may be potentially applied as electrical or aerospace devices with superior mechanical properties and high EMI shielding capacity.
There is increasing evidence that coatomer protein complex subunit beta 2 (COPB2) plays an important role in various cancer types. This study explored the role and the downstream mediators of COPB2 in prostate cancer (PCa). The expression of COPB2 was determined by the Cancer Genome Atlas database and enzyme-linked immunosorbent assay. COPB2 expression was upregulated in PCa tissues and correlated with Gleason score, biochemical recurrence, and poor prognosis. The functional roles of COPB2 in PCa were verified through a series of experiments. Knocking down COPB2 expression inhibited the growth and clonogenesis of PCa cells, promoted cell apoptosis, and inhibited the ability of scratch repair, invasion of PCa cells, and tumor growth in Nude mice. To analyze downstream signaling pathways, ingenuity pathway analysis, GSEA, and whole-genome expression spectrum GeneChip analysis were used. Western blot revealed that COPB2 expression promoted the proliferation and invasion of PCa cells by regulating the MAPK/TGF-ß signaling pathway. The interacting protein (nuclear protein 1, NUPR1) was identified via Co-IP, real-time PCR, Western blot, and TCGA database in sampled tissues. The expressions of the interaction proteins NUPR1 and COPB2 were negatively regulated by each other. COPB2 could be a new biomarker for PCa diagnosis and monitoring and to provide a theoretical basis for identifying effective drug intervention targets through in-depth mechanistic studies.
In our previous studies, we found that the rs231775 polymorphism of cytotoxic T-lymphocyte antigen 4 (CTLA-4) is associated with risks of different cancer types; however, the association remains controversial and ambiguous, so we conducted an in-depth meta-analysis to verify the association. A complete search of the PubMed, Google Scholar, Embase, Chinese databases, and Web of Science was conducted without regard to language limitations, covering all publications since November 20, 2021. The search criteria for cancer susceptibility associated with the polymorphism in the CTLA-4 gene rs231775 resulted in 87 case-control studies with 29,464 cases and 35,858 controls. The association strength was analyzed using odds ratios and 95% confidence intervals. Overall, we found that the CTLA-4 rs231775 polymorphism may reduce cancer risk. A stratified cancer type analysis showed that CTLA-4 rs231775 polymorphism was a risk factor for colorectal cancer and thyroid cancer; on the other hand, it was a protective factor for breast cancer, liver cancer, cervical cancer, bone cancer, head and neck, and pancreatic cancer. We also classified cancer into five systems and observed an increased association with digestive tract cancer, decreased associations with orthopedic tumors, tumors of the urinary system, and gynecological tumors. In the subgroup based on race, decreased relationships were observed in both Asians and Caucasians. The same decreased association was also shown in the analysis of the source of control analysis. Our present study indicates that the CTLA-4 rs231775 polymorphism contributes to cancer development and aggression.
