According to a new study published in Cancer Biology & Medicine, the inflammatory response triggered by the cytokine interleukin (IL)-6 facilitates cancer cell stemness in cholangiocarcinoma. It does this by facilitating the expression of m6A writer, a large methyltransferase complex that modifies messenger RNA and regulates gene expression.
According to Hua Ye, PhD, and the coauthors of the study, m6A modification is a targetable mediator of inflammation that is critical for the progression of cholangiocarcinoma and is an important diagnostic factor for the disease. Understanding the mechanisms regulating cell stemness in cholangiocarcinoma is of utmost importance in order to develop effective therapies for the disease.
To investigate the potential role of m6A modifications in cholangiocarcinoma cell stemness, the team of researchers used mammosphere culture assays. Using IL-6 treatment, they induced an inflammatory response and then conducted loss-of-function studies.
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They found that m6A writers were highly expressed in cholangiocarcinomas. They also found that STAT3 directly bound to the gene loci of m6A writers, exhibiting that IL-6/STAT3 signaling regulates the expression of m6A writers.
The researchers noted that downregulating m6A writers prevented cell proliferation and migration. When they did this in a mouse model, they found that cholangiocarcinoma tumorigenesis was suppressed.
The researchers wrote, “Notably, the knockdown of m6A writers inhibited [cholangiocarcinoma] cell stemness that was triggered by IL-6 treatment.” They concluded that an IL-6-triggered inflammatory response facilitates the expressions of m6A writers and cell stemness.
Cholangiocarcinoma is the second most common type of liver cancer. Cancer stem cells, a subpopulation of cancer cells capable of tumor initiation and malignant growth, play an important role in cholangiocarcinoma carcinogenesis.
Ye H, Chen T, Zeng Z, et al. The m6A writers regulated by the IL-6/STAT3 inflammatory pathway facilitate cancer cell stemness in cholangiocarcinoma. Cancer Biol Med. Published online August 4, 2021. doi:10.20892/j.issn.2095-3941.2020.0661
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