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Silencing of lncRNA AFAP1-AS1 Inhibits Cell Growth and Metastasis in Clear Cell Renal Cell Carcinoma

Zhongyi Mu*†1, Dan Dong*1, Ning Wei‡§, Mingli Sun, Wei Wang*, Yue Shao*, Jian Gao*, Ping Yin*, Chenghai Zhao*

* Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, P.R. China
† Department of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, P.R. China
‡ Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
§ Cancer Therapeutics Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA
¶ Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, P.R. China

Oncology Research 2019, 27(6), 653-661. https://doi.org/10.3727/096504018X15420748671075

Abstract

The lncRNA AFAP1-AS1, oriented from an antisense direction to the protein-coding gene AFAP1 in the opposite strand, was upregulated in a variety of tumors and associated with poor prognosis, including lung cancer, breast cancer, ovarian cancer, and so on. However, the biological role of AFAP1-AS1 in clear cell renal cell carcinoma (ccRCC) is still unknown. We observed that AFAP1-AS1 expression was significantly upregulated in ccRCC tissues and that patients with high-level expression of AFAP1-AS1 had a shorter overall survival. Knockdown of AFAP1-AS1 markedly suppressed the progression of proliferation, invasion, migration, and EMT in ccRCC cells. Downregulation of AFAP1-AS1 resulted in an increase in E-cadherin and a decrease in vimentin. Noticeably, we found that PTEN has a negative correlation with the lncRNA AFAP1-AS1 expression. Further studies verified that PTEN deficiency effectively attenuated the ability of AFAP1-AS1 in promoting ccRCC cell proliferation, invasion, migration, and EMT. Moreover, the similar biological response of silencing AFAP1-AS1 was observed in our ccRCC mice model. Knockdown of AFAP1-AS1 evidently suppressed tumor growth. Taken together, our results provide the evidences that silencing of AFAP1-AS1 inhibits cell proliferation, EMT, and metastasis through PTEN-dependent signaling, and our findings elucidate a novel potential therapeutic target or biomarker for the treatment of ccRCC.

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Cite This Article

Mu, Z., Dong, D., Wei, N., Sun, M., Wang, W. et al. (2019). Silencing of lncRNA AFAP1-AS1 Inhibits Cell Growth and Metastasis in Clear Cell Renal Cell Carcinoma. Oncology Research, 27(6), 653–661. https://doi.org/10.3727/096504018X15420748671075



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