Abstract 2103: SOX2 suppresses PTEN expression via miR-19a in esophageal squamous cell carcinoma

Abstract

Abstract We previously showed that SOX2, a master regulator during embryogenesis, is an amplification target of 3q26.33 in esophageal squamous cell carcinoma (ESCC), and that SOX2 promotes ESCC proliferation in vitro and in vivo via activation of the AKT/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. However, the mechanisms by which SOX2 promotes AKT/mTORC1 signaling remain to be elucidated. We determined that SOX2 decreased PTEN, a negative regulator of AKT signaling, via microRNA (miRNA) in ESCC cells. SOX2 knockdown increased PTEN and decreased phosphorylated AKT (p-AKT), and PTEN knockdown restored p-AKT decreased by SOX2 knockdown in SOX2 amplified ESCC cells (KYSE70, KYSE140 and TE10 cells), indicating that SOX2 elevates p-AKT via PTEN suppression in these cells. DICER knockdown increased PTEN expression without SOX2 expression change in these cells, suggesting that PTEN expression is regulated by miRNA. Therefore we hypothesized that SOX2 may suppress PTEN expression through miRNA regulation. To examine whether SOX2 modulate the expression of miRNAs, we investigated the expression of cancer-related 84 miRNAs using miRNA PCR arrays, and found that SOX2 elevated miR-17∼92 cluster (miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92) in KYSE70 cells. Quantitative RT-PCR confirmed that the expression of mir-17∼92 cluster is elevated by SOX2 in KYSE70, KYSE140, and TE10 cells. Of these miRNA, transfection of miR-19a mimic suppressed PTEN and conversely miR-19a inhibition elevated PTEN in these cells. Collectively, SOX2 may suppress PTEN expression via miR-19a in ESCC cells. Citation Format: Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Osamu Dohi, Yoshito Ito. SOX2 suppresses PTEN expression via miR-19a in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2103. doi:10.1158/1538-7445.AM2015-2103