Abstract
Lung cancer (LC) is a pulmonary malignant tumor with extremely low 5-year survival rate. N6-methyladenosine (m6A) is confirmed to regulate diverse pathophysiological processes including cancers. Methyltransferase-like 14 (METTL14) is an important RNA methyltransferase in m6A modification. However, researches on the regulatory mechanism of METTL14 on LC progression are relatively rare. Tumor xenograft experiment was conducted to investigate the effect of METTL14 on LC in vivo. The relative expression of METTL14, miR-30c-1-3p, and myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1) in LC tissues and/or cell lines was determined using qRT-PCR. Western blot assay was used to measure the protein levels of METTL14 and MARCKSL1 in tumor xenograft model and/or LC cell lines. MTT, wound healing, and transwell assays were performed to detect LC cell viability and metastasis. RNA immunoprecipitation assay and qRT-PCR were used to verify the effects of METTL14 on pri-miR-30c-1-3p. The relationship between miR-30c-1-3p and MARCKSL1 was confirmed by the dual-luciferase reporter assay. METTL14 was remarkably downregulated in LC tissues and cell lines. METTL14 mediated the maturation of miR-30c-1-3p. The overexpressed METTL14 and overexpressed miR-30c-1-3p suppressed the cell viability and metastasis in LC. Meanwhile, the increased METTL14 also repressed the growth of tumor xenograft in vivo. In addition, MARCKSL1 was confirmed to be the target gene of miR-30c-1-3p. High expression of MARCKSL1 and low expression of miR-30c-1-3p reversed the suppressive effects of METTL14 overexpression on cell viability and metastasis. METTL14 promoted the maturation of miR-30c-1-3p and mediated MARCKSL1 expression to inhibit the progression of LC. This study may provide a new insight for the LC clinical therapy.
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Conceptualization: FL and YC; Methodology: W L; Formal analysis and investigation: FL, XH, and LW; Writing-original draft preparation: FL; Writing-review and editing: WL, YC, and JZ; Funding acquisition: FL; Resources: XH and LW; Supervision: YC.
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Li, F., Zhao, J., Wang, L. et al. METTL14-Mediated miR-30c-1-3p Maturation Represses the Progression of Lung Cancer via Regulation of MARCKSL1 Expression. Mol Biotechnol 64, 199–212 (2022). https://doi.org/10.1007/s12033-021-00406-8
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DOI: https://doi.org/10.1007/s12033-021-00406-8