Human basal-like breast cancer (BLBC) is an aggressive malignancy with poor prognosis. Since most current treatments are ineffective, there is an urgent need to identify therapeutic targets for BLBC. Microfibrillar-associated protein 5 (MFAP5) plays an important role in the integration of elastic microfibers and the regulation of endothelial cell behaviors. We previously demonstrated that MFAP5 was significantly overexpressed in BLBC tissues and associated with poor metastasis-free survival of patients with BLBC. However, the detailed role of MFAP5 in BLBC is unclear. Thereby, the current study aimed to investigate the underlying function of MFAP5 in BLBC. Functional analyses were conducted for the role of MFAP5 in BLBC in vitro and in vivo. Overexpression of MFAP5 resulted in a significant increase in the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) markers in BLBC in vitro and in vivo. In addition, other metastasis animal models by tail intravenous injection of BT20 cells further confirmed that MFAP5 overexpression promoted BLBC proliferation and BT20 cells metastasis. We found that the TGF-β or Notch inhibitor significantly reversed the tumorigenicity and metastasis of MFAP5-induced BLBC cells. Our findings suggest that MFAP5 may promote EMT in BLBC metastasis via the TGF-β/Notch pathway.

Hepatocellular carcinoma (HCC) is the predominant malignant liver tumor, characterized by high morbidity, mortality, and rapid progression, and it ranks among the leading causes of cancer-related fatalities worldwide. Its treatment is facing the severe challenge of resistance to targeted drugs and immunotherapy. Bile acids (BAs) are products of cholesterol metabolism, that not only regulate lipid digestion and absorption, but also influence the development of HCC by modulating inflammation and metabolism. Dysregulation of BA metabolism is closely linked to resistance against targeted therapies and immunotherapies. BAs reduce the efficacy of targeted drugs by influencing enzymes involved in drug metabolism and drug efflux transporters, moreover, BAs also lead to immunotherapeutic resistance by regulating the formation of the immunosuppressive tumor microenvironment. Therefore, regulating BA metabolism has the potential to overcome drug resistance of targeted therapy and immunotherapy, which could be a promising treatment strategy. This review not only summarizes the roles of BA metabolism in HCC development and drug resistance, but also further explores the rationality and necessity of targeting BAs to enhance the survival of HCC patients.

Background: Autophagy is believed to participate in embryonic development, but whether the expression of autophagy-associated genes undergoes changes during the development of human embryonic kidneys remains unknown. Methods: In this work, we identified 36,151 human renal cells from embryonic kidneys of 9–18 gestational weeks in 16 major clusters by single-cell RNA sequencing (scRNA-seq), and detected 1350 autophagy-related genes in all fetal renal cells. The abundance of each cell cluster in Wilms tumor samples from scRNA-seq and GDC TARGET WT datasets was detected by CIBERSORTx. R package Monocle 3 was used to determine differentiation trajectories. Cyclone tool of R package scran was applied to calculate the cell cycle scores. R package SCENIC was used to investigate the transcriptional regulons. The FindMarkers tool from Seurat was used to calculate DEGs. GSVA was used to perform gene set enrichment analyses. CellphoneDB was utilized to analyze intercellular communication. Results: It was found that cells in the 13th gestational week showed the lowest transcriptional level in each cluster in all stages. Nephron progenitors could be divided into four subgroups with diverse levels of autophagy corresponding to different SIX2 expressions. SSBpod (podocyte precursors) could differentiate into four types of podocytes (Pod), and autophagy-related regulation was involved in this process. Pseudotime analysis showed that interstitial progenitor cells (IPCs) potentially possessed two primitive directions of differentiation to interstitial cells with different expressions of autophagy. It was found that NPCs, pretubular aggregates and interstitial cell clusters had high abundance in Wilms tumor as compared with para-tumor samples with active intercellular communication. Conclusions: All these findings suggest that autophagy may be involved in the development and cellular heterogeneity of early human fetal kidneys. In addition, part of Wilms tumor cancer cells possess the characteristics of some fetal renal cell clusters. Graphical

Hypertension is one of the known renal cell carcinoma (RCC)-associated factors. However, the gene expression patterns in hypertension tissues and the mecha