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Platinum-based chemotherapy drugs play a very important role in the treatment of patients with advanced colorectal cancer, but the drug resistance of platinum-based chemotherapy drugs is an important topic that puzzles us. If we can find mechanisms of resistance, it will be revolutionary for us. We analysed the differential genes, core genes and their enrichment pathways in platinum-resistant and non-resistant patients through a public database. Platinum-resistant cell lines were cultured in vitro for in vitro colony and Transwell analysis. Tumorigenesis analysis of nude mice in vivo. Verify the function of core genes. Through differential gene and enrichment analysis, we found that CUL4B was the main factor affecting platinum drug resistance and EMT. Our hypothesis was further verified by in vitro drug-resistant and wild-type cell lines and in vivo tumorigenesis analysis of nude mice. CUL4B leads to platinum drug resistance in colorectal cancer by affecting tumour EMT.

Oesophageal cancer ranks as one of the most common malignancy in China and worldwide. Although genome‐wide association studies and molecular biology studies aim to elucidate the driver molecules in oesophageal cancer progression, the detailed mechanisms remain to be identified. Interestingly, RNF168 (RING finger protein 168) shows a high frequency of gene amplification in oesophageal cancer from TCGA database. Here, we report an important function for RNF168 protein in supporting oesophageal cancer growth and invasion by stabilizing STAT1 protein. RNF168 gene is amplified in oesophageal cancer samples, which tends to correlate with poor prognosis. Depletion RNF168 causes decreased cell proliferation and invasion in oesophageal cancer cells. Through unbiased RNA sequencing in RNF168 depleted oesophageal cancer cell, we identifies JAK‐STAT pathway is dramatically decreased. Depletion RNF168 reduced JAK‐STAT target genes, such as IRF1, IRF9 and IFITM1. Immuno‐precipitation reveals that RNF168 associates with STAT1 in the nucleus, stabilizing STAT1 protein and inhibiting its poly‐ubiquitination and degradation. Our study provides a novel mechanism that RNF168 promoting JAK‐STAT signalling in supporting oesophageal cancer progression. It could be a promising strategy to target RNF168 for oesophageal cancer treatment.

Oestrogen receptor α (ERα) is overexpressed in two‐thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ERα ‐positive breast cancer can be effectively treated by endocrine therapy, endocrine resistance is an urgent clinical problem. Thus, further understanding of the underlying mechanisms involved in ERα signalling is critical in dealing with endocrine resistance in patients with breast cancer. In the present study, unbiased RNA sequence analysis was conducted between the MCF‐7 and MCF‐7 tamoxifen‐resistant (LCC2) cell lines in order to identify differentially expressed genes. The whole transcriptomic data indicated that the JAK‐STAT pathway is markedly up‐regulated, particularly the ISGF3 complex. As the critical effectors, STAT1 and IRF9 were up‐regulated 5‐ and 20‐fold, respectively, in LCC2 cells. The biological experiments indicated that STAT1 is important for ERα signalling. Depletion of STAT1 or inhibition of STAT1 function significantly decreased levels of ERα protein, ERα ‐target gene expression and cell proliferation in both the MCF‐7 and LCC2 cell lines. Chromatin immunoprecipitation revealed that ERα transcription is associated with STAT1 recruitment to the ERα promoter region, suggesting that transcriptional regulation is one mechanism by which STAT1 regulates ERα mRNA levels and ERα signalling in breast cancer cells. The present study reveals a possible endocrine‐resistant mechanism by which STAT1 modulates ERα signalling and confers tamoxifen resistance. Targeting of STAT1 is a potential treatment strategy for endocrine‐resistant breast cancers.

Oestrogen receptor ɑ (ERɑ) is overexpressed in two‐thirds of all breast cancers and involves in development and breast cancer progression. Although ERɑ‐positive breast cancer could be effective treated by endocrine therapy, the endocrine resistance is still an urgent clinical problem. Thus, further understanding of the underlying mechanisms ERɑ signalling is critical in dealing with endocrine resistance in breast cancer patients. MCF‐7 and T47D breast cancer cell lines are used to carry out the molecular biological experiments. Western blot is used to assess the relative protein level of ERɑ, RNF168 and actin. Real‐time PCR is used the measure the relative ERɑ‐related gene mRNA level. Luciferase assay is used to measure the relative ERɑ signalling activity. Chromatin immunoprecipitation is used to measure the RNF168 binding affinity to ERɑ promoter regions. WST assay and flow cytometry are used to measure the cell proliferation capacity. We use Student's t test and one‐way ANOVA test for statistical data analysis. Here, we report an important role in ERɑ‐positive breast cancer cells for RNF168 protein in supporting cell proliferation by driving the transcription of ERɑ. RNF168 is highly expressed in breast cancer samples, compared with normal breast tissue. In patients with breast cancer, RNF168 expression level is correlated with poor endocrine treatment outcome. Depletion of RNF168 causes decreased cell proliferation in MCF‐7 and T47D cells. Besides, depletion RNF168 reduced mRNA level of ERɑ and its target genes, such as PS2 and GREB1. Chromatin immunoprecipitation revealed that ERɑ transcription is associated with RNF168 recruitment to ERɑ promoter region, suggesting that transcriptional regulation is one mechanism by which RNF168 regulates ERɑ mRNA level and ERɑ signalling in breast cancer cells. RNF168 is required for ERɑ‐positive breast cancer cell proliferation and facilitate ERɑ signalling activity possibly through promoting transcription of ERɑ.