Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, particularly linked to chronic hepatitis B virus (HBV) infection. Recent research from Anhui Medical University has shed light on the role of interleukin 35 (IL35), illuminating its significant involvement in HBV-related HCC progression through the IL6-STAT3 signaling pathway.
HCC is particularly prevalent in regions with high HBV infection rates, with studies indicating it accounts for about 90 percent of liver cancer cases in China. The need for effective therapies is pressing, as the survival rate for HCC patients remains low due to late diagnosis and aggressive tumor behavior.
IL35, which belongs to the IL-12 cytokine family, has recently come under scrutiny for its dual role in various types of cancer, functioning both to promote and inhibit tumor growth. The study found enhanced IL35 expression levels in human HCC tissues infected with HBV, especially when triggered by the HBx protein of HBV, which is known to activate several oncogenic pathways.
The researchers effectively silenced IL35 to observe its effects on hepatoma cell lines, employing various methodologies including real-time quantitative PCR and immunohistochemistry. The results were telling; IL35 silencing significantly promoted apoptosis, halted proliferation, and impeded cell migration and invasion. These findings suggest IL35’s role as not merely passive but actively supportive of HBV-related HCC growth.
"Silencing IL-35 promoted apoptosis and suppressed proliferation, cell migration, and invasion of HBx-induced hepatoma cells," stated the authors, underscoring the potential of IL35 as a target for therapeutic intervention.
The mechanistic investigation revealed IL35 silencing leads to reduced expression of IL6, which is critically involved in the IL6-STAT3 signaling pathway—an established driver of liver cancer. This pathway's activation is frequently associated with increased cell survival and proliferation, making it a focal point for HCC pathogenesis.
Data indicated, "Knockdown of IL35 could effectively suppress the activation of the IL6-STAT3 signaling pathway," highlighting how targeting IL35 may disrupt established cancer-promoting signals within hepatocytes.
The study adds to the growing body of evidence advocating for IL35's role as not just a passenger but as an integral player within the cancer microenvironment of HBV-related HCC. Given the severity of HCC and the currently limited treatment options, this research paves the way for exploring IL35 as a novel therapeutic target.
Future research should aim to validate these findings through clinical trials and explore the specific mechanisms by which IL35 and HBV interact to contribute to HCC progression. Such investigations may offer hope for innovative treatment strategies, potentially transforming the prognosis for patients diagnosed with HBV-related HCC.