Long noncoding RNA PXN-AS1-L promotes non-small cell lung cancer progression via regulating PXN

Zhifa Zhang; Zhaohui Peng; Junying Cao; Jiaqi Wang; Yongyu Hao; Kai Song; Yan Wang; Wei Hu; Xuesong Zhang

doi:10.1186/s12935-019-0734-0

Long noncoding RNA PXN-AS1-L promotes non-small cell lung cancer progression via regulating PXN

Cancer Cell Int. 2019 Jan 22:19:20. doi: 10.1186/s12935-019-0734-0. eCollection 2019.

Authors

Zhifa Zhang^#¹, Zhaohui Peng^#^{2

3}, Junying Cao^#⁴, Jiaqi Wang⁵, Yongyu Hao¹, Kai Song¹, Yan Wang¹, Wei Hu⁶, Xuesong Zhang¹

Affiliations

¹ 1Department of Orthopaedic Surgery, the PLA General Hospital, Beijing, 100000 China.
² Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003 China.
³ 3Department of Radiology, Jinan Military General Hospital, Jinan, 250031 Shandong China.
⁴ 4Department of Ultrasonography, General Hospital of Shenyang Military Region, Shenyang, 110016 Liaoning China.
⁵ 5Department of Orthopaedic Surgery, China Medical University, Shenyang, 110001 Liaoning China.
⁶ 6Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433 China.

^# Contributed equally.

Abstract

Background: Increasingly evidences suggest that long noncoding RNAs (lncRNAs) play important roles in various cancers. LncRNA PXN-AS1-L is recently revealed to act as on oncogene in liver cancer. However, the expression, functions, and mechanisms of action of PXN-AS-L in non-small cell lung cancer (NSCLC) remain unclear.

Methods: The expression of PXN-AS1-L in primary NSCLC tissues, NSCLC bone metastasis tissues, and cell lines was measured by quantitative real-time PCR. The correlations between PXN-AS1-L expression and clinicopathological characteristics of NSCLC patients were analyzed by Pearson Chi square test and log-rank test. The roles of PXN-AS1-L in cell viability, proliferation, apoptosis, and migration of NSCLC cells, and in vivo NSCLC tumor growth were investigated by a series of gain-of-function and loss-of-function assays. The regulatory roles of PXN-AS1-L on PXN were determined by quantitative real-time PCR and western blot.

Results: PXN-AS1-L was up-regulated in NSCLC tissues compared with noncancerous lung tissues, and PXN-AS1-L was further up-regulated in NSCLC bone metastasis tissues. Increased expression of PXN-AS1-L was positively associated with advanced TNM stages and poor prognosis. Gain-of-function and loss-of-function assays showed that PXN-AS1-L increased cell viability, promoted cell proliferation, inhibited cell apoptosis, and promoted cell migration of NSCLC cells. Xenograft assays showed that PXN-AS1-L also promoted NSCLC tumor growth in vivo. Mechanistically, we found that PXN-AS1-L, as an antisense transcript of PXN, up-regulated the expression of PXN. PXN was also up-regulated in NSCLC tissues. The expression of PXN and PXN-AS1-L was positively correlated in NSCLC tissues. Furthermore, PXN knockdown attenuated the roles of PXN-AS1-L in increasing cell viability, promoting cell proliferation, inhibiting cell apoptosis, and promoting cell migration of NSCLC cells.

Conclusions: Our data revealed that PXN-AS1-L is up-regulated and acts as an oncogene in NSCLC via up-regulating PXN. Our data suggested that PXN-AS1-L might serve as a potential prognostic biomarker and therapeutic target for NSCLC.

Keywords: Long noncoding RNA; Migration; Non-small-cell lung cancer; PXN; Proliferation.