[PMC free content] [PubMed] [Google Scholar] 17. (BTG2) was defined as a downstream target of SRXN1. Mechanistic studies revealed that SRXN1\depleted reactive oxygen species (ROS) modulated migration and invasion of HCC cells. In addition, the ROS/p65/BTG2 signalling hub was found to regulate the epithelial\mesenchymal transition (EMT), which mediates the pro\metastasis role of SRXN1 in HCC cells. In vivo ABBV-4083 ABBV-4083 experiments showed SRXN1 promotes HCC tumour growth and metastasis in mouse subcutaneous xenograft and metastasis models. Collectively, our results revealed a novel pro\tumorigenic and pro\metastatic function of SRXN1 in HCC. These findings demonstrate a rationale to exploit SRXN1 as a therapeutic target effectively preventing metastasis of HCC. testanalysis. *** indicates value changes most ( em P /em ?=?2.045??10?62). These results led us to further investigate the role of BTG2 as a downstream target of SRXN1. BTG2 was previously shown to inhibit cell proliferation. 21 Some studies have pointed out that BTG2 was associated with metastasis of malignant cancers, 45 , 46 but the detailed mechanisms are not clarified. In our work, we exhibited that BTG2 suppressed EMT and metastasis in HCC Rabbit Polyclonal to DGKI tumours. SRXN1\regulated ROS modulated p65, which inhibited BTG2 expression and ultimately led to migration and invasion by HCC cells, as well as tumour metastasis in vivo. Moreover, the relationship between BTG2 and EMT was first reported in our work. Importantly, SRXN1 inhibition increased expression of BTG2 indicated that up\regulated SRXN1 might attenuate BTG2 expression, leading to increased proliferation of HCC cells. These findings will help the exploration of BTG2 as a potential tumour suppressor. However, how BTG2 inhibits EMT and promotes proliferation warrants further study. We are still investigating whether BTG2 directly interacts with molecules involved in EMT. HCC often occurs on the background of chronic liver disease, and patients are often picked up at late stages. Findings from this study would help to exploit novel drugs targets in treating malignant and advanced HCC. Additionally, in this study, we clarified how SRXN1 modulated downstream signalling to regulate HCC tumorigenesis and metastasis. But how SRXN1 is usually regulated in HCC requires further clarification. There are no studies clarifying this regulation. SRXN1 could be exploited as a drug target to inhibit metastasis and recurrence in HCC patients. Furthermore, elucidation of the functions of SRXN1 in tumorigenesis and metastasis of HCC would help to identify the functions of SRXN1 in other malignant cancers. In conclusion, we unveiled a pro\tumorigenic and pro\metastasis of SRXN1 in HCC by regulating ROS/p65/BTG2 signalling. These results provide theoretical proof for exploiting SRXN1 as a novel target for treating HCC and other malignant cancers. CONFLICT OF INTEREST The authors confirm that there are no conflicts of interest. AUTHOR CONTRIBUTION Xiufang Lv: Investigation (equal). Hailing Yu: Investigation (equal). Qianqian Zhang: Formal analysis (equal). Yongquan Huang: Methodology (equal). Xiaopeng Hong: Resources (equal). Ting Yu: Resources (equal). Huimin Lan: Methodology (equal). Chaoming Mei: Methodology (equal). Wenkai Zhang: Software (equal). Hui Luo: Conceptualization (equal); Writing\initial draft (equal); Writing\review & editing (equal). Pengfei Pang: Conceptualization (equal); Writing\initial draft (equal). Hong Shan: Funding acquisition (equal). Supporting information Fig S1 Click here for additional data file.(441K, tif) ACKNOWLEDGEMENTS We thank Mr Pengfei Yang and Wei Li for their help in IHC assays. This work was supported by the National Natural Science Foundation of China (81620108017) and the Guangdong Basic and Applied Basic Research Foundation (2020A1515011001 and 2019A1515110457). Also, this paper is usually supported by the Fundamental Research Funds for the Central Universities (Grant No. 17ykpy61 and No. 19ykpy42) ABBV-4083 and Opening Research Fund of Guangdong Provincial Key Lab of Biomedical Imaging (No. GPKLBI201909). Notes Lv X, Yu H, Zhang Q, et al. SRXN1 stimulates hepatocellular carcinoma tumorigenesis ABBV-4083 and metastasis through modulating ROS/p65/BTG2 signalling. J Cell Mol Med. 2020;24:10714C10729. 10.1111/jcmm.15693 [PMC free article] [PubMed] [CrossRef] [Google Scholar] Xiufang Lv and Hailing Yu contributed equally to this work. Contributor Information Hui Luo, Email: nc.ude.usys.liam@35houl. Pengfei Pang, Email: nc.ude.usys.liam@fpgnap. DATA AVAILABILITY.
