Emerging role and function of SPDL1 in human health and diseases.

SPDL1 (spindle apparatus coiled-coil protein 1), also referred to as CCDC99, is a recently identified gene involved in cell cycle regulation. SPDL1 encodes a protein, hSpindly, which plays a critical role in the maintenance of spindle checkpoint silencing during mitosis. hSpindly coordinates microtubule attachment by promoting kinesin recruitment and mitotic checkpoint signaling. Moreover, the protein performs numerous biological functions in vivo and its aberrant expression is closely associated with abnormal neuronal development, pulmonary interstitial fibrosis, and malignant tumor development. In this review, we provide an overview of studies that reveal the characteristics of SPDL1 and of the protein encoded by it, as well as its biological and tumor-promoting functions.

Mechanism of bufalin inhibition of colon cancer liver metastasis by regulating M2-type polarization of Kupffer cells induced by highly metastatic colon cancer cells.

Patients with metastatic colorectal cancer often have poor outcomes, primarily due to hepatic metastasis. Colorectal cancer (CRC) cells have the ability to secrete cytokines and other molecules that can remodel the tumor microenvironment, facilitating the spread of cancer to the liver. Kupffer cells (KCs), which are macrophages in the liver, can be polarized to M2 type, thereby promoting the expression of adhesion molecules that aid in tumor metastasis. Our research has shown that huachanshu (with bufalin as the main active monomer) can effectively inhibit CRC metastasis. However, the underlying mechanism still needs to be thoroughly investigated. We have observed that highly metastatic CRC cells have a greater ability to induce M2-type polarization of Kupffer cells, leading to enhanced metastasis. Interestingly, we have found that inhibiting the expression of IL-6, which is highly expressed in the serum, can reverse this phenomenon. Notably, bufalin has been shown to attenuate the M2-type polarization of Kupffer cells induced by highly metastatic Colorectal cancer (mCRC) cells and down-regulate IL-6 expression, ultimately inhibiting tumor metastasis. In this project, our aim is to study how high mCRC cells induce M2-type polarization and how bufalin, via the SRC-3/IL-6 pathway, can inhibit CRC metastasis. This research will provide a theoretical foundation for understanding the anti-CRC effect of bufalin.

Global trends in bufalin application research for cancer from 2003 to 2022: A bibliometric and visualised analysis.

Background: Bufalin, the main active ingredient of the traditional Chinese medicine huachansu, is used in the clinical treatment of colorectal cancer and has multiple effects, including the inhibition of migratory invasion, reversal of multi-drug resistance, induction of apoptosis and differentiation, and inhibition of angiogenesis. Methods: We collected relevant articles on bufalin from 2003 to 2022 using the Web Science platform, and analysed the information using VOSviewer, CiteSpace, and Microsoft Excel to categorise and summarise the publications over the past 20 years. Results: We collected 371 papers, with a steady increase in the number of articles published globally. China has the highest number of published articles, whereas Japan has the highest number of citations. Currently, there is considerable enthusiasm for investigating the anti-tumour mechanism of bufalin and optimising drug delivery systems for its administration. Conclusion: For the first time, we present a comprehensive overview of papers published worldwide on bufalin over the past two decades and the progress of its application in tumour therapy. We summarised the key authors, institutions, and countries that have contributed to the field and the potential of bufalin for the treatment of cancer. This will help other researchers obtain an overview of progress in the field, enhance collaboration and knowledge sharing, and promote future research on bufalin.

DPM2 serve as novel oncogene and prognostic marker transactivated by ESR1 in breast cancer.

Breast cancer (BRCA) is the most common malignancies worldwide with increasing rate. Dolichol phosphate mannose synthase (DPMS) is a critical mannosyltransferase involved in the posttranslational modification of proteins. At present, there is limited knowledge regarding the function of DPMS in breast cancer. In this study, silica analysis in multiple datasets found that dolichyl-phosphate mannosyltransferase subunit 2 (DPM2) is an unfavorable prognostic marker, suggesting its oncogenic role. Cell counting kit-8 and apoptosis assays show that DPM2-silenced cancer cells exhibit decreased growth potential and enhanced cell death rate. Further, transwell and wound healing assays show reduced invasion and migration capabilities in DPM2 knockdown groups, xenograft nude mice model demonstrated smaller tumor volume in DPM2 silenced BC cells. Then, the underlying downstream mechanism of DPM2 in BC was predicted and analyzed, highlighting classical tumorigenic pathways like JAK/STAT signaling pathway and oxidative phosphorylation activated in the cancer group. Finally, ChIP-seq analysis, expression correlation analysis, inhibitor treatment, and dual luciferase assays show that DPM2 is transcriptionally activated by estrogen receptor1 (ESR1). The results show that high expression of DPM2 mRNA is significantly correlated with shorter overall survival (OS) and disease-free survival (DFS) in breast cancer patients, and in vitro knockdown of DPM2 can significantly inhibit the malignant phenotypes of cells, including proliferation, invasion, migration, and apoptosis. These results suggest that DPM2 may play an important role in breast cancer. Altogether, we first uncovered the tumorigenic and prognostic role of DPM2 in breast cancer, cellular assays, and bioinformatics analysis highlighted DPM2 as oncogene via inhibited cancer-related signaling pathways in breast cancer. Besides, DPM2 is transcriptionally activated by ESR1, the signaling axis of ESR1/DPM2 provides a new strategy for BC-targeted therapy.

The relationship between cadmium exposure and hepatitis B susceptibility and the establishment of its prediction model.

Cadmium, a common metal, is an environmental contaminant that is hepatotoxic and immunotoxic. Cadmium exposure may affect hepatitis B immunity. The purpose of this study was to assess the association between cadmium exposure and hepatitis B serology in the US population and to develop a model to predict susceptibility of hepatitis B. The study included 50,588 individuals in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Univariate and multivariate logistic regression and dose-response curves were used to evaluate the relationship between cadmium exposure and hepatitis B serology. Through multivariate logistic regression results, a predictive model was established, and relevant indicators were used to verify the clinical value of the model and evaluate prognostic value of serum cadmium concentration in patients with hepatitis B. We selected 5989 (≥ 6 years old) participants. Univariate logistic regression analysis showed that gender (aOR = 0.7192, 95% CI = 0.6492-0.7968), age (aOR = 1.030, 95% CI = 1.026-1.033), race (aOR = 0.8974, 95% CI = 0.8591-0.9374), poverty ratio (aOR = 1.042, 95% CI = 0.9872-1.101), body mass index (BMI) (aOR = 1.052, 95% CI = 1.044-1.061), hypertension (aOR = 2.017, 95% CI = 1.763-2.306), diabetes (aOR = 2.673, 95% CI = 2.119-3.370), vigorous recreational activities (aOR = 0.6369, 95% CI = 0.5725-0.7085), moderate recreational activity (aOR = 0.7681, 95% CI = 0.6935-0.8574) and cadmium (aOR = 1.295, 95% CI = 1.168-1.436) were closely related to hepatitis B virus (HBV) susceptibility. After adjusting for these confounding factors, multivariate logistic regression analysis showed that the odds ratio of HBV susceptibility was positively correlated with the level of cadmium in serum. The effectiveness of the model was then evaluated by establishing a nomogram, and by calibration curves, ROC curves, and clinical decision curves. Our study shows that cadmium exposure is positively associated with HBV susceptibility risk in the US population, and the constructed model has clinical significance.

LINC00665 activating Wnt3a/ß-catenin signaling by bond with YBX1 promotes gastric cancer proliferation and metastasis.

Long noncoding RNAs (lncRNAs) play a key role in human cancer development; nevertheless, the effect of lncRNA LINC00665 on the progression of gastric cancer (GC) still unclear. In this study, we found that LINC00665 expression is upregulated in GC than normal gastric mucosa tissues and higher LINC00665 expression is associated with a poor prognosis in GC patients. Downregulated LINC00665 inhibited GC cells proliferation, invasion, and migration in vitro. Pulmonary metastasis animal models showed that downregulated LINC00665 could reduce the lung metastasis of GC in vivo. Tumor organoids were generated from human malignant GC tissues, downregulated LINC00665 could inhibit the growth of the organoids of GC tissues. Mechanistically, downregulated LINC00665 could inhibit GC cells EMT. RNA pulldown, RIP, and RIP-seq studies found that LINC00665 can bind to the transcription factor YBX1 and form a positive feed-forward loop. The luciferase reporter and CHIP results showed that YBX1 could regulate the transcriptional activity of Wnt3a, and downregulation of LINC00665 could block the activation of Wnt/ß-catenin signaling. In conclusion, our results identified a feedback loop between LINC00665 and YBX1 that activates Wnt/ß-catenin signaling, and it may be a potential therapeutic approach to suppress GC progression.