Introduction: The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. The PcG mainly consists of two complexes, PRC1 and Polycomb Repressive Complex 2 (PRC2). Polycomb-like 2 (PCL2) is known to interact with the PRC2 protein. The role of PCL2 in the development and progression of glioma is unclear. Methods: We use The Cancer Genome Atlas (TCGA) database to detect the expression of PCL2 in various tumors. 117 cases of clinical glioma (WHOI–IV) were collected, and PCL2 expression and localization were detected by immunohistochemical staining. Glioma cells U87/U251 were infected with overexpressed and interfered PCL2. CCK8 assay, colony formation assay, EdU method, cell cycle and apoptosis were used to detect cell proliferation and apoptosis. Western blot was used to detect the expression of PRC2-related core proteins. After DZNeP intervention, PRC2 protein expression was again measured to discuss the mechanism of PCL2 action. Results: TCGA database results and immunohistochemical staining results suggest that PCL2 is highly expressed in gliomas. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. The overexpression of PCL2 upregulated the expression levels of EZH2 and EED (two core members of PRC2), decreased the expression of SUZ12, increased the level of H3K27 trimethylation (H3K27me3), H3K4 dimethylation (H3K4me2), and decreased H3K9 dimethylation (H3K9me2). The result after interfering with PCL2 was the opposite. Conclusions: As an important accessory protein of PRC2, PCL2 can not only change the expression of PRC2 components, but also affect the expression level of Histone methylation. Therefore, PCL2 may be an important hub for regulating the synergy among PRC2 members. This study revealed PCL2 as a new target for tumor research and open up a new avenue for future research in glioma.

Among all malignancies worldwide, gastric cancer is the fifth most common cancer with the third highest mortality rate. One of the main reasons for the low survival rate is the recurrence and metastasis that occurs in many patients after surgery. Numerous studies have shown that abnormal TRIM33 expression is associated with the progression of malignant tumors. TRIM33 can function either as a tumor suppressor or tumor promoter in different cancers. Our data showed that TRIM33 was highly expressed in stomach cancer, and in human gastric cancer tissues, low expression of TRIM33 was associated with poor prognosis in patients with gastric cancer. To clarify the function of TRIM33 in survival and epithelial–mesenchymal transition in gastric cancer cells, we investigated the effect of TRIM33 knockdown in several gastric cancer cell lines. Downregulation of TRIM33 in BGC-823 and SGC-7901 cells enhanced the proliferation, colony formation, and migratory ability of these gastric cancer cells. It also promoted epithelial–mesenchymal transition; transfection of cells with siRNA targeting TRIM33 led to the upregulation of vimentin and N-Cadherin expression, and downregulation of E-Cadherin expression. Meanwhile, the transforming growth factor beta pathway was activated: levels of transforming growth factor beta were elevated and the expressions of p-Smad2, Smad2, Smad3, and Smad4 were activated. To confirm the role of TRIM33 in vivo, a xenograft model was established in nude mice. Immunohistochemical analysis identified that the protein levels of TRIM33, p-Smad2, Smad2, Smad3, Smad4, vimentin, and N-Cadherin were increased, and E-Cadherin levels were decreased, in xenograft tumors from the si-TRIM33 group. Taken together, these results suggest that TRIM33 may be a potential marker for the diagnosis and prognosis of gastric cancer. Furthermore, it may also serve as a novel target for gastric cancer treatment.

Isocitrate dehydrogenase1 (IDH1) mutation is the most important genetic change in glioma. The most common IDH1 mutation results in the amino acid substitution of arginine 132 (Arg/R132), which is located at the active site of the enzyme. IDH1 Arg132His (R132H) mutation can reduce the proliferative rate of glioma cells. Numerous diseases follow circadian rhythms, and there is growing evidence that circadian disruption may be a risk factor for cancer in humans. Dysregulation of the circadian clock serves an important role in the development of malignant tumors, including glioma. Brain‑Muscle Arnt‑Like protein 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) are the main biological rhythm genes. The present study aimed to further study whether there is an association between IDH1 R132H mutation and biological rhythm in glioma, and whether this affects the occurrence of glioma. The Cancer Genome Atlas (TCGA) database was used to detect the expression levels of the biological rhythm genes BMAL1 and CLOCK in various types of tumor. Additionally, U87‑MG cells were infected with wild‑type and mutant IDH1 lentiviruses. Colony formation experiments were used to detect cell proliferation in each group, cell cycle distribution was detected by flow cytometry and western blotting was used to detect the expression levels of wild‑type and mutant IDH1, cyclins, biological rhythm genes and Smad signaling pathway‑associated genes in U87‑MG cells. TCGA database results suggested that BMAL1 and CLOCK were abnormally expressed in glioma. Cells were successfully infected with wild‑type and mutant IDH1 lentiviruses. Colony formation assay revealed decreased cell proliferation in the IDH1 R132H mutant group. The cell cycle distribution detected by flow cytometry indicated that IDH1 gene mutation increased the G₁ phase ratio and decreased the S phase ratio in U87‑MG cells. The western blotting results demonstrated that IDH1 R132H mutation decreased the expression levels of the S phase‑associated proteins Cyclin A and CDK2, and increased the expression levels of the G₁ phase‑associated proteins Cyclin D3 and CDK4, but did not significantly change the expression levels of the G₂/M phase‑associated protein Cyclin B1. The expression levels of the positive and negative rhythm regulation genes BMAL1, CLOCK, period (PER s (PER1, 2 and 3) and cryptochrom (CRY)s (CRY1 and 2) were significantly decreased, those of the Smad signaling pathway‑associated genes Smad2, Smad3 and Smad2‑3 were decreased, and those of phosphorylated (p)‑Smad2, p‑Smad3 and Smad4 were increased. Therefore, the present results suggested that the IDH1 R132H mutation may alter the cell cycle and biological rhythm genes in U87‑MG cells through the TGF‑β/Smad signaling pathway.

3‑deazaneplanocin A (DZNep) is a histone methyltransferase inhibitor, which may cause the reactivation of silenced tumor suppressor genes in tumors to inhibit the development, metastasis and dissemination of tumor cells. However, the effects and mechanisms of its application in gastric cancer remain unclear. The present study revealed an inhibitory function of DZNep in BGC‑823 cells. The cell colony, Cell Counting Kit‑8 (CCK8), wound healing, Transwell and flow cytometry assays were performed, and the results demonstrated that DZNep could inhibit the proliferation, apoptosis and invasion of BGC‑823 cells, and promote their apoptosis. The effects of intervention in BDC‑823 cells with DZNep on the RNA and protein expression levels of hypoxia‑inducible factor (Hif‑1α) and Wnt/β‑catenin signalling molecules were further examined using reverse transcription‑quantitative PCR and western blot analysis. The results demonstrated that different concentrations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif‑1α, total β‑catenin and phosphorylated‑β‑catenin and increase the expression levels of non‑phosphorylated‑β‑catenin to different degrees. The results of the present study suggests that DZNep inhibits BGC‑823 gastric cancer cells via the inhibition of EZH2, Hif‑1α and Wnt/β‑catenin signalling molecules. These results provide theoretical basis for the application of DZNep in clinical trials.

Understanding oncogenic processes and underlying mechanisms to advance research into human tumors is critical for effective treatment. Studies have shown that Metal regulatory transcription factor 2（MTF2) drives malignant progression in liver cancer and glioma. However, no systematic pan-cancer analysis of MTF2 has been performed. Here, we use University of California Santa Cruz, Cancer Genome Atlas , Genotype-Tissue Expression data, Tumor Immune Estimation Resource, and Clinical Proteomic Tumor Analysis Consortium bioinformatics tools to explore differential expression of MTF2 across different tumor types. MTF2 was found to be highly expressed in the cancer lines that were available through the respective databases included in the study, and overexpression of MTF2 may lead to a poor prognosis in tumor patients such as glioblastoma multiforme, brain lower grade glioma, KIPAN, LIHC, adrenocortical carcinoma, etc. We also validated MTF2 mutations in cancer, compared MTF2 methylation levels in normal and primary tumor tissues, analyzed the association of MTF2 with the immune microenvironment, and validated the functional role of MTF2 in glioma U87 and U251 and breast cancer MDA-MB-231 cell lines by cytometry. This also indicates that MTF2 has a promising application prospect in cancer treatment.