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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.


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.


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.

cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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