N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors. However, despite its undeniable importance, comprehensive research on the key m6A methyltransferase METTL5 in colorectal cancer (CRC) remains limited. Here, researchers found that METTL5 is significantly upregulated in both CRC cells and tissues and is significantly associated with poor prognosis. In vitro experiments clearly confirmed the oncogenic effect of METTL5, further supported by its ability to promote CRC cell proliferation, invasion, and migration. Notably, researchers discovered that TLR8 is a downstream target of METTL5, and downregulation of TLR8 significantly inhibited CRC cell proliferation, invasion, and tumor growth.
In CRC cell lines, researchers first used PCR to detect TLR8 mRNA expression, which showed that TLR8 expression in CRC cell lines was generally higher than in normal colorectal mucosal epithelial cells. Subsequently, they constructed stable TLR8 knockdown cell lines. CCK-8 assays showed that TLR8 downregulation significantly inhibited CRC cell proliferation (Figure 1I and J). They used Transwell assays to evaluate the effects of TLR8 on CRC cell invasion and migration. Results showed that in the TLR8 knockdown HCT-116 and HT-29 cell lines, CRC cell invasion and migration were significantly reduced compared to the control group (Figure 1K and L). Scratch assays yielded similar results (Figure 1M and N).
Figure 1. TLR8 is identified as a downstream target of METTL5 and an oncogenic protein in colorectal cancer. (Kong L S, et al., 2024)