The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway.

Cisplatin (DDP) is commonly used in the treatment of non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD), and the primary cause for its clinical inefficacy is chemoresistance. Here, we aimed to investigate a novel mechanism of chemoresistance in LUAD cells, focusing on the calcium-sensing receptor (CaSR). In this study, high CaSR expression was detected in DDP-resistant LUAD cells, and elevated CaSR expression is strongly correlated with poor prognosis in LUAD patients receiving chemotherapy. LUAD cells with high CaSR expression exhibited decreased sensitivity to cisplatin, and the growth of DDP-resistant LUAD cells was inhibited by cisplatin treatment in combination with CaSR suppression, accompanied by changes in BRCA1 and cyclin B1 protein expression both in vitro and in vivo. Additionally, an interaction between CaSR and KIF11 was identified. Importantly, suppressing KIF11 resulted in decreased protein levels of BRCA1 and cyclin B1, enhancing the sensitivity of DDP-resistant LUAD cells to cisplatin with no obvious decrease in CaSR. Here, our findings established the critical role of CaSR in promoting cisplatin resistance in LUAD cells by modulating cyclin B1 and BRCA1 and identified KIF11 as a mediator, highlighting the potential therapeutic value of targeting CaSR to overcome chemoresistance in LUAD.

TMEM176B Promotes EMT via FGFR/JNK Signalling in Development and Tumourigenesis of Lung Adenocarcinoma.

Lung cancer, the leading cause of cancer-related incidence and mortality worldwide, is characterised by high invasiveness and poor prognosis. Novel therapeutic targets are required, especially for patients with inoperable metastatic disease requiring systemic therapies to improve patients' welfare. Recently, studies indicated that TMEM176B is a positive regulator in breast and gastric cancers, and it could be a potential target for treatment. In this study, we used single-cell sequencing, proteomics, Co-IP, and in vivo and in vitro experimental models to investigate the role of TMEM176B in lung adenocarcinoma development. Our study indicated that TMEM176B expression was enhanced in lung adenocarcinoma tissues, and it was associated with shorter overall survival (OS). TMEM176B promoted cellular functions, including cell proliferation, invasion, migration and adhesion in vitro and tumour growth in vivo. Moreover, the tube formation ability of endothelial cells was enhanced by treating with the tumour cell-conditioned medium. We have also demonstrated that TMEM176B regulated EMT via the FGFR1/JNK/Vimentin/Snail signalling cascade. Overall, our study suggests TMEM176B could be a potential therapeutic target in lung adenocarcinoma.

Magnesium Depletion Score and Metabolic Syndrome in US Adults: Analysis of NHANES 2003-2018.

BACKGROUND: The association between magnesium status and metabolic syndrome remains unclear. This study aimed to examine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and metabolic syndrome among US adults. METHODS: We analyzed data from 15,565 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. Weighted univariate and multivariate logistic regression were used to assess the association between MDS and metabolic syndrome. Restricted cubic spline analysis was conducted to characterize dose-response relationships. Stratified analyses by sociodemographic and lifestyle factors were also performed. RESULTS: In both univariate and multivariate analyses, higher MDS was significantly associated with increased odds of metabolic syndrome. Each unit increase in MDS was associated with approximately a 30% higher risk for metabolic syndrome, even after adjusting for confounding factors (OR 1.31; 95% CI 1.17-1.45). Restricted cubic spline graphs depicted a linear dose-response relationship across the MDS range. This positive correlation remained consistent across various population subgroups and exhibited no significant interaction by age, gender, race, adiposity, smoking status, or alcohol consumption. CONCLUSIONS: Higher urinary magnesium loss as quantified by MDS may be an independent linear risk factor for metabolic syndrome in US adults, irrespective of sociodemographic and behavioral factors. Optimizing magnesium nutritional status could potentially confer benefits to patients with metabolic syndrome.

Emerging trends and research foci of berberine on tumor from 2002 to 2021: A bibliometric article of the literature from WoSCC.

Background: Cancer, also known as a malignant tumor, is caused by the activation of oncogenes, which leads to the uncontrolled proliferation of cells that results in swelling. According to the World Health Organization (WHO), cancer is one of the main causes of death worldwide. The main variables limiting the efficacy of anti-tumor treatments are side effects and drug resistance. The search for natural, safe, low toxicity, and efficient chemical compounds in tumor research is essential. Berberine is a pentacyclic isoquinoline quaternary ammonium alkaloid isolated from Berberis and Coptis that has long been used in clinical settings. Studies in recent years have reported the use of berberine in cancer treatment. In this study, we performed a bibliometric analysis of berberine- and tumor-related research. Materials and methods: Relevant articles from January 1, 2002, to December 31, 2021, were identified from the Web of Science Core Collection (WOSCC) of Clarivate Analytics. Microsoft Excel, CiteSpace, VOSviewer, and an online platform were used for the literary metrology analysis. Results: A total of 1368 publications had unique characteristics. Publications from China were the most common (783 articles), and Y. B. Feng (from China) was the most productive author, with the highest total citations. China Medical University (Taiwan) and Sun Yat-sen University (China) were the two organizations with the largest numbers of publications (36 each). Frontiers in Pharmacology was the most commonly occurring journal (29 articles). The present body of research is focused on the mechanism, molecular docking, and oxidative stress of berberine in tumors. Conclusion: Research on berberine and tumors was thoroughly reviewed using knowledge map and bibliometric methods. The results of this study reveal the dynamic evolution of berberine and tumor research and provide a basis for strategic planning in cancer research.

RNA methylation and cancer treatment.

To this date, over 100 different types of RNA modification have been identified. Methylation of different RNA species has emerged as a critical regulator of transcript expression. RNA methylation and its related downstream signaling pathways are involved in plethora biological processes, including cell differentiation, sex determination and stress response, and others. It is catalyzed by the RNA methyltransferases, is demethylated by the demethylases (FTO and ALKBH5) and read by methylation binding protein (YTHDF1 and IGF2BP1). Increasing evidence indicates that this process closely connected to cancer cell proliferation, cellular stress, metastasis, immune response. And RNA methylation related protein has been becoming a promising targets of cancer therapy. This review outlines the relationship between different types of RNA methylation and cancer, and some FTO inhibitors in cancer treatment.