Pinin Contributes to ccRCC Progression and Resistance to Sunitinib-Induced Apoptosis

YU Xiao¹, LIU Kaitai², XIANG Zhenfei², LIN Chen¹, ZHANG Yanru¹, WANG Ping¹*, MA Qi³^*

(¹Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China; ²Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China; ³3Translational Research Laboratory for Urology, the Key Laboratory of Ningbo City, Ningbo First Hospital, Ningbo 315010, China)

Abstract:

The expression and bio-function of desomosome-related proteins have been gradually disclosed in various human cancers. PNN (pinin) is a desmosome-associated molecule that has been well studied in epithelial cell-cell adhesion and RNA alternative splicing, which suggests its involvement in cancer progression. However, little is known about the association between PNN expression and ccRCC (clear cell renal cancer cell) tumorigenesis. This study reported that the expression of PNN was significantly increased in ccRCC tissues and cells, and the elevated level of PNN was closely associated with pathological grade of patients with ccRCC. Suppression of PNN expression inhibited cell proliferation and cell viability, inducing G₀/G₁ cell cycle arrests. Furthermore, si-PNN treatment significantly enhanced the cytotoxic effect of sunitinib and the apoptotic cell number compared with cells underwent sunitinib treatment only. The molecular signals for this phenomenon involved the PNN-mediated activation of PI3K/AKT pathway. In conclusion, these results reveals that PNN contributes to ccRCC progression and resistance to targeted drug-induced apoptosis via maintaining PI3K/AKT activation and may become a potential

CSTR: 32200.14.cjcb.2020.09.0007