<p>Matrine is considered as an anti-cancer drug in a variety of cancers, including colorectal cancer (CRC). Methyltransferase-like 14 (METTL14) and Mex-3 RNA binding family member A (MEX3A) were associated with CRC progression. This study focused on the mechanism of matrine with METTL14 and MEX3A in CRC.&#xa0;Cell viability, proliferation, apoptosis, and migration/invasion were assessed by cell counting kit-8, EdU assay, flow cytometry, and transwell assay. Glycolysis metabolism was evaluated by glucose consumption and ATP/ADP ratio using kits. RT-qPCR and Western blot were employed for expression examination. Gene interaction was analyzed via methylated RNA immunoprecipitation (MeRIP) and RIP assays. The role of matrine in vivo was explored by xenograft models in mice.&#xa0;CRC cell proliferation, metastasis and glycolysis were restrained by matrine. METTL14 was up-regulated in matrine-treated CRC cells. Anti-tumor effects of matrine on CRC cells were associated with upregulation of METTL14. METTL14 reduced MEX3A expression by mediating the m6A modification of MEX3A, and YTHDF1 acted as a “reader” protein to affect m6A methylation of MEX3A. METTL14 suppressed CRC cell malignant progression via inhibiting MEX3A. MEX3A overexpression recused the tumor-inhibitory regulation of matrine in CRC cells. Matrine also repressed tumor growth of CRC in vivo through downregulating MEX3A.&#xa0;This study revealed that matrine played a cancer-suppressive role in CRC through targeting METTL14/MEX3A network, unraveling a molecular mechanism of matrine in CRC inhibition.</p>

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Matrine functions as a tumor inhibitor to influence proliferation, metastasis and glycolysis in colorectal cancer via depending on METTL14-mediated m6A methylation of MEX3A

  • Tao Meng,
  • Zhengjie Gao,
  • Xiangjie Fang,
  • Jun Liu,
  • Dong Hou,
  • Lanfang Zhang,
  • Zhichao Zuo,
  • Zhi Zheng,
  • Shaohui Zhu

摘要

Matrine is considered as an anti-cancer drug in a variety of cancers, including colorectal cancer (CRC). Methyltransferase-like 14 (METTL14) and Mex-3 RNA binding family member A (MEX3A) were associated with CRC progression. This study focused on the mechanism of matrine with METTL14 and MEX3A in CRC. Cell viability, proliferation, apoptosis, and migration/invasion were assessed by cell counting kit-8, EdU assay, flow cytometry, and transwell assay. Glycolysis metabolism was evaluated by glucose consumption and ATP/ADP ratio using kits. RT-qPCR and Western blot were employed for expression examination. Gene interaction was analyzed via methylated RNA immunoprecipitation (MeRIP) and RIP assays. The role of matrine in vivo was explored by xenograft models in mice. CRC cell proliferation, metastasis and glycolysis were restrained by matrine. METTL14 was up-regulated in matrine-treated CRC cells. Anti-tumor effects of matrine on CRC cells were associated with upregulation of METTL14. METTL14 reduced MEX3A expression by mediating the m6A modification of MEX3A, and YTHDF1 acted as a “reader” protein to affect m6A methylation of MEX3A. METTL14 suppressed CRC cell malignant progression via inhibiting MEX3A. MEX3A overexpression recused the tumor-inhibitory regulation of matrine in CRC cells. Matrine also repressed tumor growth of CRC in vivo through downregulating MEX3A. This study revealed that matrine played a cancer-suppressive role in CRC through targeting METTL14/MEX3A network, unraveling a molecular mechanism of matrine in CRC inhibition.