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Background & Aims Cholangiocarcinoma (CCA) is a malignant tumour originating from the biliary epithelium that easily infiltrates, metastasizes and recurs. The deficiency of FBXO31 facilitates the initiation and progression of several types of cancer. However, the involvement of FBXO31 in CCA progression has remained unclear. Methods qRT‐PCR was used to detect the expression of FBXO31 in CCA. The biological functions of FBXO31 were confirmed in vivo and in vitro. Sphere formation and flow cytometry were used to identify the stem cell properties of CCA. Results FBXO31 is downregulated in CCA and that deficiency of FBXO31 is associated with the TNM stage of CCA. Functional studies showed FBXO31 inhibits cell growth, migration, invasion, cancer stem cell (CSC) properties and epithelial‐mesenchymal transition (EMT) in vitro and impedes tumour growth in vivo. In addition, overexpression of FBXO31 increases the cisplatin (CDDP) sensitivity of CCA cells. RNA‐sequencing analysis revealed that FBXO31 is involved in redox biology and metal ion metabolism in CCA cells during CDDP treatment. Further studies revealed that FBXO31 enhances ferroptosis induced by CDDP in CCA and CSC‐like cells. FBXO31 enhances ubiquitination of glutathione peroxidase 4 (GPX4), which leads to proteasomal degradation of GPX4. Moreover, overexpression of GPX4 compromises the promoting effects of FBXO31 on CDDP‐induced ferroptosis in CCA and CSC‐like cells. Conclusions Our studies indicate that FBXO31 functions as a tumour suppressor in CCA and sensitizes CSC‐like cells to CDDP by promoting ferroptosis and facilitating the proteasomal degradation of GPX4.

To explore the effect of curcumol on autophagy and ferroptosis of hepatic stellate cells, and to clarify the molecular mechanism of its anti-hepatic fibrosis. In the present study, we report that curcumol promotes the death of activated HSCs and reduces the deposition of extracellular matrix. Interestingly, curcumol treatment can trigger ferroptosis to eliminate activated HSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation.Curcumol promotes HSC autophagy, which may be the key mechanism for its induction of ferroptosis. It is worth noting that the upregulation of nuclear receptor coactivator 4 (NCOA4) may play a key molecular mechanism. NCOA4 mediates the release of iron ions and induces the occurrence of ferroptosis. Overall, curcumol promotes autophagy in hepatic stellate cells, mediates the degradation of NCOA4 and FTH1 complexes, releases iron ions, leads to iron overload, and induces ferroptosis, which may be an important mechanism for its anti-hepatic fibrosis effect.

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Butyrylation plays a crucial role in the cellular processes. Due to limit of techniques, it is a challenging task to identify histone butyrylation sites on a large scale. To fill the gap, we propose an approach based on information entropy and machine learning for computationally identifying histone butyrylation sites. The proposed method achieves 0.92 of area under the receiver operating characteristic (ROC) curve over the training set by 3-fold cross validation and 0.80 over the testing set by independent test. Feature analysis implies that amino acid residues in the down/upstream of butyrylation sites would exhibit specific sequence motif to a certain extent. Functional analysis suggests that histone butyrylation was most possibly associated with four pathways (systemic lupus erythematosus, alcoholism, viral carcinogenesis and transcriptional misregulation in cancer), was involved in binding with other molecules, processes of biosynthesis, assembly, arrangement or disassembly and was located in such complex as consists of DNA, RNA, protein, etc. The proposed method is useful to predict histone butyrylation sites. Analysis of feature and function improves understanding of histone butyrylation and increases knowledge of functions of butyrylated histones.