C-MYC and BCL-2 mediate YAP-regulated tumorigenesis in OSCC

// Xiyan Chen 1, 2, * , Weiting Gu 3, * , Qi Wang 1, 2 , Xucheng Fu 1, 2 , Ying Wang 1, 2 , Xin Xu 1, 2 and Yong Wen 1, 2 1 School of Stomatology, Shandong University, Jinan, China 2 Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China 3 Qilu Hospital of Shandong University, Jinan, China * These authors contributed equally to this work Correspondence to: Yong Wen, email: wenyong@sdu.edu.cn Keywords: yes-associated protein(YAP); oral squamous cell carcinoma (OSCC); C-MYC; BCL-2; tumorigenesis Received: August 20, 2017      Accepted: November 17, 2017      Published: December 07, 2017 ABSTRACT Transcriptional co-activator Yes-associated protein (YAP) is a key oncogene in mammalian cells. The present understanding of YAP in oral squamous cells carcinoma (OSCC) remains unclear. The purpose of this study is to investigate the effects of YAP on proliferation and apoptosis in OSCC and the molecular mechanism. The results showed the expression level of YAP was higher in OSCC tissues than that in adjacent normal tissues. Knockdown of YAP in CAL27 cell lines prohibited cell proliferation while augmented apoptosis. Conversely, overexpression of YAP protected cells from apoptosis and promoted cell proliferation. Moreover, C-MYC and BCL-2 mRNA and protein levels were altered due to the differential expression of YAP. Subsequent Verteporfin treatment in CAL27 cells revealed that the transcription and translation of BCL-2 and C-MYC both decreased. In a tumor xenograft model, knockdown of YAP suppressed tumor growth of CAL27 in vivo , while YAP overexpression promoted the tumor growth. These results suggest that YAP is a crucial regulator that exerts pro-proliferation and anti-apoptosis effects in OSCC through actions affecting the cell cycle and intrinsic apoptotic signaling. Thus YAP could potentially serve as a valuable molecular biomarker or therapeutic target in the treatment of OSCC.