FEAT enhances INSL3 expression in testicular Leydig cells

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2018-11, Vol.23 (11), p.952-962
• Main Authors: Li, Yan, Kobayashi, Kyosuke, Murayama, Kosho, Kawahara, Kohichi, Shima, Yuichi, Suzuki, Akira, Tani, Kenzaburo, Takahashi, Atsushi
• Format: Article
• Language: English
• Subjects: Adenosine kinase; AMP; Animals; Cell Movement; Cilia; Cryptorchidism; Cryptorchidism - metabolism; Cryptorchidism - pathology; Fetuses; Immunoblotting; Immunofluorescence; Immunohistochemistry; Insulin; Insulin - genetics; Insulin - metabolism; Kinases; Leydig cells; Leydig Cells - cytology; Leydig Cells - metabolism; Male; Methyltransferase; Methyltransferases - metabolism; Mice; Protein kinase; Proteins; Proteins - genetics; Proteins - metabolism; siRNA; Testes; Testis - cytology; Testis - metabolism; Transcriptional Activation; Tumor cells; Tumorigenesis
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12644

FEAT, the protein encoded by methyltransferase‐like 13 (METTL13), is aberrantly upregulated in most human cancers and potently drives tumorigenesis in vivo; however, its role in normal tissues remains elusive. Immunoblotting has displayed weak FEAT expression in normal human tissues, including the testis. Here, we found that FEAT is expressed in fetal and adult Leydig cells in the testis. FEAT knockdown using siRNA increased primary cilia formation in MA‐10 Leydig tumor cells, accompanied by enhanced 5′ adenosine monophosphate‐activated protein kinase (AMPK) activation. Immunofluorescence analyses of FEAT‐silenced MA‐10 cells showed diminished insulin‐like factor 3 (INSL3) expression. A male Mettl13+/− mouse developed bilateral intraabdominal cryptorchidism, suggesting defective INSL3 production by fetal Leydig cells. Leydig cells from the mouse showed markedly decreased INSL3 protein by immunohistochemistry. Together, these results suggest that FEAT facilitates the INSL3 production in testicular Leydig cells that is essential for transabdominal testis migration. FEAT (METTL13) is expressed in fetal and adult Leydig cells in the testis. FEAT‐silenced MA‐10 Leydig cells showed diminished INSL3 protein. A male Mettl13+/− mouse exhibited bilateral intraabdominal cryptorchidism and markedly decreased INSL3 expression in Leydig cells.