Husna, Amity University Kolkata
What is Hepatocellular carcinoma (HCC)?
Hepatocellular carcinoma (HCC) is cancer in the liver. It is the most common type of primary liver cancer that occurs mostly in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. Hepatocellular carcinoma (HCC) is a digestive malignant tumour, capable of spreading to adjacent tissues with poor clinical outcomes. It accounts for the second leading cause of cancer death globally. For many years, major advances have been obtained for understanding the epidemiologic risk factors as well as the molecular mechanisms that lead to the formation of HCC tumours or the HCC tumorigenesis.
Role of ATF2 and MARCH6 proteins in Hepatocellular carcinoma (HCC):
Protein ubiquitination is an important modification at the post-transcriptional level, and it plays a role in regulating protein stability. According to evidence, protein ubiquitination is involved in series of processes, including endocytosis, DNA repair, signal transduction, and tumorigenesis. Ubiquitin is ligated to its specific substrate with the help of E3 ligases. Membrane-associated ring-CH-type finger (MARCH) proteins are a subfamily of the RING-type E3 ubiquitin ligase. Most of the MARCH family members are specified to be involved in the development of human diseases. More recently, studies have shown that MARCH6 and E3 ubiquitin ligase play a versatile role in the regulation of cholesterol homeostasis in hepatocytes. However, the specific role of MARCH6 in Hepatocellular carcinoma (HCC) remains unclear.
Activating transcription factor 2 (ATF2) is a transcription factor that can regulate the expression of a wide range of genes involved in cell survival, proliferation, growth, apoptosis, and DNA damage response, so it plays a very important role in the progression of cancer. For instance, ATF2 functions as an oncogene in different types of cancer, including breast cancer, melanoma, lung cancer, and colorectal cancer. It is a well-known fact that ATF2 contributes to carcinogenesis by regulating the expression of downstream targets but the upstream modulator of ATF2 and its significance in HCC is yet to be understood.
Recent study: A recent study by BMC Cancer explored the role of MARCH6 and ATF2 in Hepatocellular carcinoma (HCC) development. MARCH 6 knockdown and overexpressing HCC cells were constructed. HCC cell proliferation, migration, and tumorigenesis were also examined.
Results of the study:
- MARCH6 has been highly expressed in the human Hepatocellular carcinoma (HCC) cells: Immunohistochemical staining of MARCH6 was performed. It was found that survival, as well as disease-free survival rates, were lower in HCC patients who had a high level of MARCH6 protein compared to those who had a low level of MARCH6. Moreover, MARCH6 was up-regulated in HCC tissues when compared to the adjacent normal samples.
- The expression of MARCH6 was checked in three different HCC cell lines. The expressions collectively suggested that MARCH6 has an oncogenic function in HCC cells.
- It was found that MARCH6 silencing leads to a reduction in the growth of tumours in HCC cells which means MARCH6 is essential for HCC growth.
- ATF2 over-expression also restored the growth and migration capacity of the HCC cell line which suggests that MARCH6 up-regulation of ATF2 contributes to HCC cell growth and migration.
- Conversely, down-regulation of ATF2 reverses the growth and promoting role of MARCH6 over-expression on the migration capacity of HCC cells. Collectively, MARCH6/ATF2 has an essential role in HCC cell growth and migration.
Conclusion and significance of the study:
In conclusion, this study shows that MARCH6 is overexpressed in HCC which promotes the progressive and invasive ability of HCC cells by enhancing the expression of ATF2, this also suggests that ectopic MARCH6 expression might be an important driver for HCC development. Thus, MARCH6 proves to be a promising target for the diagnosis and treatment of Hepatocellular carcinoma (HCC).
Also read: Rats have an ingroup bias similar to humans
Source: Sun, Jie, et al. “MARCH6 Promotes Hepatocellular Carcinoma Development through Up-Regulation of ATF2.” BMC Cancer, vol. 21, no. 1, July 2021, p. 827. BioMed Central, doi:http://10.1186/s12885-021-08540-x.
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About the Author: Husna is an undergraduate student of BTech Biotechnology at Amity University Kolkata. She is a research enthusiast in Immunology and Immunotherapy but she has a keen interest in various other Bioscience subjects as well. She is constantly focused on improving her knowledge and laboratory skills through various internships. She is a Scientific content writer who has knowledge in diverse backgrounds of Biotechnology.
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