Abstract
Inhibitors of the CDK family of proteins have been approved for the treatment of a variety of tumours; however, the development of new drugs administered in combination with CDK inhibitors is expected to improve the therapeutic effect. We identified the function of suppressor of cytokine signalling 1 (SOCS1) in hepatocellular carcinoma (HCC) cell models and the xenograft mouse model. When SOCS1 expression was artificially upregulated, HCC cell lines were arrested at the G1-S transition in the cell cycle. Interestingly, during this process, total CyclinD1 protein increased, but the effective proportion decreased. We found that the deficiency of CyclinD1 in the nucleus is probably due to the decrease in the stability of nuclear CyclinD1 caused by the ubiquitin-based degradation of P21, thus inhibiting the progression of the cell cycle to S phase. After P21 expression was increased, the levels of the component that inactivates CyclinD1 decreased as expected. It showed that P21 has a partial promoting effect on cancer. SOCS1 is a good indicator of prognosis, tumour size and long-term survival after resection. SOCS1 is expected to become a drug target in combined with CDK family inhibitors.
Highlights
In 2018, liver cancer became the sixth most common cancer in the world and the fourth highest cause of cancer-related death, with approximately 841000 new cases and 782000 deaths each year
As consistently shown by qRT-Polymerase Chain Reaction (PCR) and Western blot, suppressor of cytokine signalling 1 (SOCS1) was minimally expressed in most hepatocellular carcinoma (HCC) cells (Figure 1E), indicating that the SOCS1 level is associated with the cancer suppressor phenotype in HCC cell lines
Based on the downregulation of SOCS1 expression in liver cancer specimens from the Oncomine database and the detection of SOCS1 in primary clinical specimens, we propose that SOCS1 plays an important role in the occurrence and development of HCC
Summary
In 2018, liver cancer became the sixth most common cancer in the world and the fourth highest cause of cancer-related death, with approximately 841000 new cases and 782000 deaths each year. Most patients with HCC have middle or advanced stage disease at the time of diagnosis. Some of these patients www.aging-us.com are eligible for liver transplantation, and the health care centres that perform these procedures have safely and effectively expanded liver transplantation candidates on the basis of Milan standards [3]. There are still many patients with inoperable cancer, but the advent of molecular targeting therapies in recent years has greatly improved the overall survival of these patients [4]. It is of great significance to develop more effective molecular targeting drugs in combination with current treatment methods to improve the curative effect and prolong the survival of HCC patients
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