High Expression of Long Noncoding RNA PCNA-AS1 Promotes Non-Small-Cell Lung Cancer Cell Proliferation and Oncogenic Activity via Upregulating CCND1

Chuanyong Wu^1,2,*, Xiao-ting Zhu^3,*, Lei Xia⁴, Lin Wang¹, Wenjun Yu¹, Qiaomei Guo¹, Mingna Zhao¹, Jiatao Lou^1✉

1. Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
2. Department of Laboratory Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
3. Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
4. Department of orthopedics, Hospital of No.83 army, Xinxiang, 453000, China.
*These authors contributed equally to this work.

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Citation:
Wu C, Zhu Xt, Xia L, Wang L, Yu W, Guo Q, Zhao M, Lou J. High Expression of Long Noncoding RNA PCNA-AS1 Promotes Non-Small-Cell Lung Cancer Cell Proliferation and Oncogenic Activity via Upregulating CCND1. J Cancer 2020; 11(7):1959-1967. doi:10.7150/jca.39087. Available from https://www.jcancer.org/v11p1959.htm

Abstract

Accumulating evidences showed that aberrantly expressed long noncoding RNAs (lncRNAs) have critical roles in many cancers. However, the expression and roles of a poorly studied lncRNA PCNA-AS1 in non-small-cell lung cancer (NSCLC) remain unknown. In this study, we investigated the expression, clinical significance, biological roles, and functional mechanism of PCNA-AS1 in NSCLC. Our results showed that PCNA-AS1 was upregulated in NSCLC tissues and cell lines, and correlated with TNM stages. Functional experiments showed that overexpression of PCNA-AS1 promoted NSCLC cell proliferation and cell cycle progression. Depletion of PCNA-AS1 inhibited NSCLC cell proliferation and cell cycle progression, and also inhibited NSCLC tumor growth in vivo. Mechanistically, we found that PCNA-AS1 upregulated CCND1 expression. The expression of PCNA-AS1 was positively correlated with that of CCND1 in NSCLC tissues. Moreover, depletion of CCND1 abrogated the oncogenic roles of PCNA-AS1 in NSCLC. In conclusion, highly expressed PCNA-AS1 promotes NSCLC cell proliferation and oncogenic activity via upregulating CCND1. Our results imply that PCNA-AS1 might serve as a therapeutic target for NSCLC.

Keywords: long noncoding RNA, PCNA-AS1, non-small-cell lung cancer, proliferation, cell cycle, CCND1