Br J Cancer: Inhibiting CBX4 can effectively inhibit the production of sorafinia resistance in liver cancer cells

Hepatocellular carcinoma (HCC) is the world's third leading cause of cancer-related deaths (8.2% of all cancer-related deaths), and its incidence increases year by year and has a high mortality rate.
because of the early diagnosis difficulties of HCC, and high recurrence rate, postoperative metastasis and chemotherapy resistance also make the survival rate of patients lower.
oral multi-kinase inhibitor Sorafenib is considered a first-line systemic treatment option for patients with advanced liver cancer.
, although the average total survival (OS) of patients with the therapy increased significantly, higher drug resistance significantly limited the benefits of Sorafini therapy.
previous studies have shown that the abunding of tumor stem cells (CSCs) may increase patient resistance to sorafinie in the years after initial treatment.
, however, it is not clear how CSC affects the role of soraphini in liver cancer, and the molecular mechanism and regulatory effect of CSC on liver cancer resistance have yet to be clarified.
, exploring the development and evolution of targeted resistance is important to improve the efficacy of chemotherapy for liver cancer.
CBX4 (chromosomal box 4) is located on chromosome 17q25.3 and encodes the CBX4 protein as a member of the PcG protein family.
pcG protein is a transcriptional deterrent that is mainly involved in regulating development, aging, stem cell properties and cancer development.
previous studies have shown that high levels of CBX4 expression correspond to the OS period in patients with poor liver cancer, suggesting that CBX4 is an independent prognostic factor for liver cancer, and evidence suggests that CBX4 may play a vital role in maintaining CSC for liver cancer.
the study aims to explore the potential role of inhibiting CBX4-regulated cancer stem cells (CSCs) and to assess their contribution to Solafinib resistance in advanced liver cancer (HCC).
researchers in the
miR424-CBX4 affect tumor growth in the Sorafini resistance transplant tumor model used HCC cell line and solafinie drug-resistant transplant tumor mouse models to analyze the effects of miR424 on CSC characteristics.
analysis of RNA expression in HCC cancer patients and Sorrafne resistance (SR) cell lineages through RT-PCR and second-generation sequencing, respectively, to validate key microRNAs and targets in the relevant networks.
researchers found that microRNA and mRNA spectromety of SR cell line showed that miR424 and its direct target CBX4 were significantly associated with stem cell characteristics, poor survival rates, and clinical characteristics.
, miR424 was able to inhibit the nuclear transport of the YAP1 protein induced by CBX4 and CBX4, but was independent of protein production.
when CA3 and UNC3866 were used to regulate the expression of YAP1 and CBX4, the tumor-like and dryness of cells were greatly inhibited, indicating that these compounds have a strong anti-tumor effect on SR HCC cells.
the relevant regulatory pathpolysis diagrams, the results show that blocking the expression of CBX4 is essential to inhibit the development of soraphine resistance for advanced liver cancer.