Mingyuan Wang

MLLT11-TRIL complex promotes the progression of endometrial cancer through PI3K/AKT/mTOR signaling pathway

Endometrial cancer (EC) is a gynecological malignant tumor characterized by high incidence. EC occurrence and development are regulated by numerous molecules and signal pathways. There is a need to explore key regulatory molecules to identify potential therapeutic targets to reduce the incidence of EC. Treatment by targeting a single molecule is characterized by poor efficacy owing to the development of resistance and significant side effects. The current study explored potential candidates in EC by integrating bioinformatics analysis and in vivo and in vitro experimental validation to circumvent the limitation of low efficacy of currently used molecules. Molecular dynamics simulations provide details at the molecular level of intermolecular regulation. In the current study, MLLT11 and TRIL were identified as important regulatory molecules in EC. The two molecules formed a heteromultimer by binding to AKT protein, which induced its phosphorylation of threonine at position 308. Ultimately, the complex stimulates PI3K/AKT/mTOR signaling pathway, a pivotal pathway in tumors. The findings of the current study show a novel complex, MLLT11-TRIL, which can act as AKT protein agonist, thus inducing activity of PI3K/AKT/mTOR signaling pathway. Targeting MLLT11 and TRIL simultaneously, or blocking the formation of the MLLT11-TRIL complex, can abrogate progression of EC.

Curcumin: a natural organic component that plays a multi-faceted role in ovarian cancer

AbstractCurcumin, a natural organic component obtained from Curcuma longa’s rhizomes, shows abundant anti-tumor, antioxidant and anti-inflammatory pharmacological activities, among others. Notably the anti-tumor activity has aroused widespread attention from scholars worldwide. Numerous studies have reported that curcumin can delay ovarian cancer (OC), increase its sensitivity to chemotherapy, and reduce chemotherapy drugs’ side effects. It has been shown considerable anticancer potential by promoting cell apoptosis, suppressing cell cycle progression, inducing autophagy, inhibiting tumor metastasis, and regulating enzyme activity. With an in-depth study of curcumin’s anti-OC mechanism, its clinical application will have broader prospects. This review summarizes the latest studies on curcumin’s anti-OC activities, and discusses the specific mechanism, hoping to provide references for further research and applications.

Systematic prediction of key genes for ovarian cancer by co‐expression network analysis

AbstractOvarian cancer (OC) is the most lethal gynaecological malignancy, characterized by high recurrence and mortality. However, the mechanisms of its pathogenesis remain largely unknown, hindering the investigation of the functional roles. This study sought to identify key hub genes that may serve as biomarkers correlated with prognosis. Here, we conduct an integrated analysis using the weighted gene co‐expression network analysis (WGCNA) to explore the clinically significant gene sets and identify candidate hub genes associated with OC clinical phenotypes. The gene expression profiles were obtained from the MERAV database. Validations of candidate hub genes were performed with RNASeqV2 data and the corresponding clinical information available from The Cancer Genome Atlas (TCGA) database. In addition, we examined the candidate genes in ovarian cancer cells. Totally, 19 modules were identified and 26 hub genes were extracted from the most significant module (R2 = .53) in clinical stages. Through the validation of TCGA data, we found that five hub genes (COL1A1, DCN, LUM, POSTN and THBS2) predicted poor prognosis. Receiver operating characteristic (ROC) curves demonstrated that these five genes exhibited diagnostic efficiency for early‐stage and advanced‐stage cancer. The protein expression of these five genes in tumour tissues was significantly higher than that in normal tissues. Besides, the expression of COL1A1 was associated with the TAX resistance of tumours and could be affected by the autophagy level in OC cell line. In conclusion, our findings identified five genes could serve as biomarkers related to the prognosis of OC and may be helpful for revealing pathogenic mechanism and developing further research.

TAF1A and ZBTB41 serve as novel key genes in cervical cancer identified by integrated approaches

AbstractCervical cancer (CC) is the second most common cancer and the leading cause of cancer mortality in women. Numerous studies have found that the development of CC was associated with multiple genes. However, the mechanisms on gene level are enigmatic, hindering the understanding of its functional roles. This study sought to identify prognostic biomarkers of CC, and explore their biological functions. Here we conducted an integrated analysis to screen potential vital genes. Candidate genes were further tested by experiments in clinical specimens and cancer cell line. Then, molecular modeling was used to predict the three-dimensional structure of candidate genes’ proteins, and the interaction pattern was analyzed by docking simulation technique. Among the potential genes identified, we found that TAF1A and ZBTB41 were highly correlated. Furthermore, there was a definite interaction between the proteins of TAF1A and ZBTB41, which was affected by the activity of the p53 signaling pathway. In conclusion, our findings identified TAF1A and ZBTB41 could serve as biomarkers of CC. We confirmed their biological function and deciphered their interaction for the first time, which may be helpful for developing further researches.