| Title: |
KIAA1429/VIRMA promotes breast cancer progression by m6A‐dependent cytosolic HAS2 stabilization. |
| Authors: |
Li, Na, Zhu, Zhouting, Deng, Yufei, Tang, Rachel, Hui, Hui, Kang, Yuqi, Rana, Tariq M |
| Source: |
EMBO Reports; 10/9/2023, Vol. 24 Issue 10, p1-17, 17p |
| Abstract: |
N6‐methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, plays important roles in many physiological and pathological processes, including the development and progression of cancer. RNA modification by m6A is regulated by methyltransferases, demethylases, and m6A‐binding proteins that function in large part by regulating mRNA expression and function. Here, we investigate the expression of m6A regulatory proteins in breast cancer. We find that expression of KIAA1429/VIRMA, a component of the m6A methyltransferase complex, is upregulated in breast cancer tissue and correlates positively with poor survival. KIAA1429/VIRMA is mislocalized to the cytosol of breast cancer tissues and cell lines, and shRNA‐mediated knockdown inhibits breast cancer cell proliferation, migration, and invasion. Mechanistically, KIAA1429/VIRMA is shown to bind to the m6A‐dependent RNA‐binding protein insulin‐like growth factor 2 mRNA‐binding protein 3 (IGF2BP3), leading to recruitment and stabilization of m6A‐modified hyaluronan synthase 2 (HAS2) mRNA. HAS2 mRNA and KIAA1429/VIRMA mRNA levels correlate positively in breast cancer tissues, suggesting that the KIAA1429/VIRMA–IGF2BP3–HAS2 axis promotes breast cancer growth and contributes to poor prognosis. Synopsis: The m6A methyltransferase complex component KIAA1429/VIRMA is upregulated and mislocalized to the cytosol in breast cancer tissues and cell lines. A KIAA1429/VIRMA–IGF2BP3–HAS2 axis promotes breast cancer growth and might contribute to poor prognosis. Expression and cytosolic distribution of KIAA1429/VIRMA are elevated in breast cancer tissue and cell lines.KIAA1429/VIRMA depletion reduces HAS2 mRNA m6A levels, RNA stability, and expression.Cytosolic KIAA1429/VIRMA interacts with m6A binder IGF2BP3 and enhances HAS2 mRNA expression.HAS2 plays an essential role for KIAA1429/VIRMA‐mediated breast cancer cell proliferation and migration. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
