METTL3-mediated m6A modification of KIF3C-mRNA promotes prostate cancer progression and is negatively regulated by miR-320d

Abstract

The occurrence of distant metastasis is one of the leading causes of death in patients with prostate cancer (PCa). It is confirmed that kinesin protein is associated with a variety of malignancies, and the KIF3 family is related to cancer, but the relationship between KIF3C and prostate cancer is not clear. Our experiments have confirmed that KIF3C is highly expressed in prostate cancer tissues and cell lines. Further, functional tests have proven that KIF3C can promote the growth migration and invasion of PCa. We used Starbase 3.0 to discover that methyltransferase like 3 (METTL3) interacts with KIF3C. Our hypothesis and experiments concluded that METTL3 induced m6A modification on KIF3C, promoting the stabilization of KIF3C-mRNA by IGF2 binding protein 1 (IGF2BP1). The prediction that miR-320d inhibits KIF3C expression by targeting METTL3 using the miRmap website, was later confirmed experimentally. Further, a recovery experiment was used to confirm that miR-320d inhibited the progression of prostate cancer. KIF3C was overexpressed in prostate cancer, promoting its growth migration and invasion was induced by miR-320d/METTL3 in an m6A dependent process.

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer

“…A later study also shows that IGF2BP1 promotes tumorigenesis and metastasis of oral squamous cell carcinoma via enhancing Bmi1 mRNA translation in METTL3-mediated m 6 A modification manner 146 . A subsequent study shows that METTL3 promotes the mRNA stability of kinesin-like protein, KIP3C in IGF2BP1- modified m 6 A manner, accelerating prostate cancer progression 147 . Moreover, METTL3 methylates KRT7-AS to enhance the mRNA stability of keratin 7 (KRT7) depending on IGF2BP1-modified m 6 A, promoting breast cancer lung metastasis 148 .…”

KIF3C Promotes the Malignant Progression of Lung Cancer Cells A549

“…We found that KIF3C expression was upregulated in non-small cell lung cancer cells and tissues and promoted the proliferation and metastasis of lung cancer cells. The expression of KIF3C was also found to be negatively regulated by miR-150-5p and miR-186-3p [19] . Dysregulation of PI3K/AKT signaling pathway has been demonstrated in both, tumor and non-tumor diseases.…”

Role of m6A writers, erasers and readers in cancer

“…Prostate cancer is the second most common cancer in men and the fifth leading cause of cancer deaths, with approximately 1.4 million new cases and 375,000 deaths each year [ 176 ]. Studies showed that METTL3 regulates LEF1 [ 199 ], KIF3C [ 200 ], USP4 [ 201 ], GLI1 [ 202 ], ITGB1 [ 170 ], IGF1R [ 203 ], and lncRNA PCAT6 [ 203 ] expression in an m6A-dependent manner to promote prostate cancer malignant progression. One study showed that knocking out METTL3 drives prostate cancer cell resistance to androgen receptor antagonists; hence, the change in m6A abundance may be a mechanism underlying treatment resistance in metastatic prostate cancer [ 43 ].…”