N7-methylguanosine (m7G) is one of the most prevalent post-transcriptional modifications of RNA and plays a critical role in RNA translation and stability. As a pivotal m7G regulator, methyltransferase-like 1 (METTL1) is responsible for methyl group transfer during the progression of m7G modification and contributes to the structure and functional regulation of RNA. Accumulating evidence in recent years has revealed that METTL1 plays key roles in various diseases depending on its m7G RNA methyltransferase activity. Elevated levels of METTL1 are typically associated with disease development and adverse consequences. In contrast, METTL1 may act as a disease suppressor in several disorders. While the roles of m7G modifications in disease have been extensively reviewed, the critical functions of METTL1 in various types of disease and the potential targeting of METTL1 for disease treatment have not yet been highlighted. This review describes the various biological functions of METTL1, summarises recent advances in understanding its pathogenic and disease-suppressive functions and discusses the underlying molecular mechanisms. Given that METTL1 can promote or inhibit disease processes, the possibility of applying METTL1 inhibitors and agonists is further discussed, with the goal of providing novel insights for future disease diagnosis and potential intervention targets.
Metachronous liver metastases (MLM) are characterised by high incidence and high mortality in clinical colorectal cancer treatment. Currently traditional clinical methods cannot effectively predict and prevent the occurrence of metachronous liver metastasis in colorectal cancer. Based on 5hmC-Seal analysis of blood and tissue samples, this study found that portal venous blood was more relevant to tumour gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using the 10 5hmC epigenetic alterations, to accurately distinguish MLM patients from patients without metastases. Among these epigenetic alterations, phosphodiesterase 4 (PDE4D) was highly increased in MLM patients and correlated with poor survival. Moreover, our studies demonstrated that PDE4D was a key metastasis-driven target for drug development. Interfering with the function of PDE4D significantly repressed liver metastases. Similarly, roflumilast, a PDE4 inhibitor for chronic obstructive pulmonary disease (COPD) therapy, also inhibits liver metastases. Further studies indicate that blocking the function of PDE4D can affect CRC invasion through the HIF-1α-CCN2 pathway. To develop a more efficient PDE4 inhibitor and reduce the occurrence of adverse events, we also designed several new compounds based on 2-arylbenzofurans and discovered lead L11 with potent affinity for PDE4D and significant suppression of liver metastases. In this work, our study provides a promising strategy for predicting metachronous liver metastasis and discovers L11 as a potential repurposed drug for inhibiting liver metastasis, which have the potential to benefit patients with CRC in the future.
Dear editor,
We are writing this letter to apply for an erratum of our published paper by Wu et al. We sincerely apologize for the mistakes and deeply regret any inconvenience this may have caused you.
Original version of Figure 5
The red block highlights the incorrect image of Vector control group.
The new version of Figure 5
A correct image of the vector control group (3 M) is included in Figure 5C.
The amended Figure 5
The reason for correction:
I recently discovered an error in Figure 5 while reviewing my paper. In the original version of Figure 5C, for 3 months after virus injection (upper panel), the image from Vector control group was inadvertently replaced by hTau group. Upon reviewing the original data, we realized that the mistake was made by inadvertently duplicated the layers during figure preparation. We have now included the correct image of Vector control group in the amended Figure 5. There were no significant differences in ChAT+ signals between the vector and overexpressing hTau groups (3 months). The experimental conclusions remain unchanged by this revision; therefore, no adjustments to the article's text are necessary.
Thank you for your consideration. We look forward to your kind response.
Sincerely yours,
Dr. Dongqin Wu
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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