Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | NSCLC | Primary research

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

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

Published in: Cancer Cell International | Issue 1/2019

Login to get access

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.
Literature
1.
2.
Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014;14:535–46.CrossRef
3.
Reck M, Heigener DF, Mok T, Soria JC, Rabe KF. Management of non-small-cell lung cancer: recent developments. Lancet. 2013;382:709–19.CrossRef
4.
Sekimoto N, Suzuki Y, Sugano S. Decreased KPNB1 expression is induced by PLK1 inhibition and leads to apoptosis in lung adenocarcinoma. J Cancer. 2017;8:4125–40.CrossRef
5.
Samulin Erdem J, Skaug V, Haugen A, Zienolddiny S. Loss of MKK3 and MK2 copy numbers in non-small cell lung cancer. J Cancer. 2016;7:512–5.CrossRef
6.
Boldrini L, Giordano M, Niccoli C, Melfi F, Lucchi M, Mussi A, Fontanini G. Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma. Cancer Cell Int. 2017;17:105.CrossRef
7.
Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015;47:199–208.CrossRef
8.
Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell. 2016;29:452–63.CrossRef
9.
Yan X, Hu Z, Feng Y, Hu X, Yuan J, Zhao SD, Zhang Y, Yang L, Shan W, He Q, et al. Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell. 2015;28:529–40.CrossRef
10.
Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, Liu F, Pan W, Wang TT, Zhou CC, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25:666–81.CrossRef
11.
Battaglin F, Naseem M, Puccini A, Lenz HJ. Molecular biomarkers in gastro-esophageal cancer: recent developments, current trends and future directions. Cancer Cell Int. 2018;18:99.CrossRef
12.
Ivanovic RF, Viana NI, Morais DR, Silva IA, Leite KR, Pontes-Junior J, Inoue G, Nahas WC, Srougi M, Reis ST. miR-29b enhances prostate cancer cell invasion independently of MMP-2 expression. Cancer Cell Int. 2018;18:18.CrossRef
13.
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.CrossRef
14.
Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15:7–21.CrossRef
15.
Flintoft L. Non-coding RNA: structure and function for lncRNAs. Nat Rev Genet. 2013;14:598.PubMed
16.
Liu X, Xiao ZD, Han L, Zhang J, Lee SW, Wang W, Lee H, Zhuang L, Chen J, Lin HK, et al. LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Nat Cell Biol. 2016;18:431–42.CrossRef
17.
Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152:1298–307.CrossRef
18.
Xu D, Yang F, Yuan JH, Zhang L, Bi HS, Zhou CC, Liu F, Wang F, Sun SH. Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/beta-catenin signaling. Hepatology. 2013;58:739–51.CrossRef
19.
Zhang C, Yuan J, Hu H, Chen W, Liu M, Zhang J, Sun S, Guo Z. Long non-coding RNA CHCHD4P4 promotes epithelial-mesenchymal transition and inhibits cell proliferation in calcium oxalate-induced kidney damage. Braz J Med Biol Res. 2017;51:e6536.PubMedPubMedCentral
20.
Lin A, Hu Q, Li C, Xing Z, Ma G, Wang C, Li J, Ye Y, Yao J, Liang K, et al. The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors. Nat Cell Biol. 2017;19:238–51.CrossRef
21.
Lin A, Li C, Xing Z, Hu Q, Liang K, Han L, Wang C, Hawke DH, Wang S, Zhang Y, et al. The LINK-A lncRNA activates normoxic HIF1alpha signalling in triple-negative breast cancer. Nat Cell Biol. 2016;18:213–24.CrossRef
22.
Zhu XT, Yuan JH, Zhu TT, Li YY, Cheng XY. Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3. FEBS J. 2016;283:3739–54.CrossRef
23.
Li JK, Chen C, Liu JY, Shi JZ, Liu SP, Liu B, Wu DS, Fang ZY, Bao Y, Jiang MM, et al. Long noncoding RNA MRCCAT1 promotes metastasis of clear cell renal cell carcinoma via inhibiting NPR3 and activating p38-MAPK signaling. Mol Cancer. 2017;16:111.CrossRef
24.
Parasramka M, Yan IK, Wang X, Nguyen P, Matsuda A, Maji S, Foye C, Asmann Y, Patel T. BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma. Mol Cancer. 2017;16:22.CrossRef
25.
Fernando TR, Contreras JR, Zampini M, Rodriguez-Malave NI, Alberti MO, Anguiano J, Tran TM, Palanichamy JK, Gajeton J, Ung NM, et al. The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia. Mol Cancer. 2017;16:126.CrossRef
26.
Mizrahi I, Mazeh H, Grinbaum R, Beglaibter N, Wilschanski M, Pavlov V, Adileh M, Stojadinovic A, Avital I, Gure AO, et al. Colon cancer associated transcript-1 (CCAT1) expression in adenocarcinoma of the stomach. J Cancer. 2015;6:105–10.CrossRef
27.
Zhang L, Yang F, Yuan JH, Yuan SX, Zhou WP, Huo XS, Xu D, Bi HS, Wang F, Sun SH. Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma. Carcinogenesis. 2013;34:577–86.CrossRef
28.
Hosseini ES, Meryet-Figuiere M, Sabzalipoor H, Kashani HH, Nikzad H, Asemi Z. Dysregulated expression of long noncoding RNAs in gynecologic cancers. Mol Cancer. 2017;16:107.CrossRef
29.
Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73:1180–9.CrossRef
30.
Wan L, Sun M, Liu GJ, Wei CC, Zhang EB, Kong R, Xu TP, Huang MD, Wang ZX. Long noncoding RNA PVT1 promotes non-small cell lung cancer cell proliferation through epigenetically regulating LATS2 expression. Mol Cancer Ther. 2016;15:1082–94.CrossRef
31.
Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, Xia R, Xu TP, Jin FY, Liu ZJ, et al. Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition. Mol Cancer. 2014;13:68.CrossRef
32.
Su W, Feng S, Chen X, Yang X, Mao R, Guo C, Wang Z, Thomas DG, Lin J, Reddy RM, et al. Silencing of long non-coding RNA MIR22HG triggers cell survival/death signaling via oncogenes YBX1, MET, and p21 in lung cancer. Cancer Res. 2018;78:3207–19.CrossRef
33.
Mao C, Wang X, Liu Y, Wang M, Yan B, Jiang Y, Shi Y, Shen Y, Liu X, Liai W, et al. A G3BP1-interacting lncRNA promotes ferroptosis and apoptosis in cancer via nuclear sequestration of p53. Cancer Res. 2018;78:3484–96.CrossRef
34.
Yuan S, Liu Q, Hu Z, Zhou Z, Wang G, Li C, Xie W, Meng G, Xiang Y, Wu N, et al. Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma. Cell Death Dis. 2018;9:450.CrossRef
35.
Li K, Sun D, Gou Q, Ke X, Gong Y, Zuo Y, Zhou JK, Guo C, Xia Z, Liu L, et al. Long non-coding RNA linc00460 promotes epithelial-mesenchymal transition and cell migration in lung cancer cells. Cancer Lett. 2018;420:80–90.CrossRef
36.
Chen Z, Li JL, Lin S, Cao C, Gimbrone NT, Yang R, Fu DA, Carper MB, Haura EB, Schabath MB, et al. cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth. J Clin Invest. 2016;126:2267–79.CrossRef
37.
White NM, Cabanski CR, Silva-Fisher JM, Dang HX, Govindan R, Maher CA. Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer. Genome Biol. 2014;15:429.CrossRef
38.
Yuan JH, Liu XN, Wang TT, Pan W, Tao QF, Zhou WP, Wang F, Sun SH. The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1. Nat Cell Biol. 2017;19:820–32.CrossRef
39.
Jiang H, Zhang H, Hu X, Li W. Knockdown of long non-coding RNA XIST inhibits cell viability and invasion by regulating miR-137/PXN axis in non-small cell lung cancer. Int J Biol Macromol. 2018;111:623–31.CrossRef
40.
Wu DW, Chen CY, Chu CL, Lee H. Paxillin confers resistance to tyrosine kinase inhibitors in EGFR-mutant lung cancers via modulating BIM and Mcl-1 protein stability. Oncogene. 2016;35:621–30.CrossRef
41.
Bi Y, Han Y, Bi H, Gao F, Wang X. miR-137 impairs the proliferative and migratory capacity of human non-small cell lung cancer cells by targeting paxillin. Hum Cell. 2014;27:95–102.CrossRef
42.
Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16:203–22.CrossRef
43.
Slack FJ. Tackling tumors with small RNAs derived from transfer RNA. N Engl J Med. 2018;378:1842–3.CrossRef
44.
Huang C, Rajfur Z, Borchers C, Schaller MD, Jacobson K. JNK phosphorylates paxillin and regulates cell migration. Nature. 2003;424:219–23.CrossRef
45.
Liu S, Thomas SM, Woodside DG, Rose DM, Kiosses WB, Pfaff M, Ginsberg MH. Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature. 1999;402:676–81.CrossRef
Metadata
Title
Long noncoding RNA PXN-AS1-L promotes non-small cell lung cancer progression via regulating PXN
Authors
Zhifa Zhang
Zhaohui Peng
Junying Cao
Jiaqi Wang
Yongyu Hao
Kai Song
Yan Wang
Wei Hu
Xuesong Zhang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0734-0

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue

Primary research

Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α

Primary research

Interfering cellular lactate homeostasis overcomes Taxol resistance of breast cancer cells through the microRNA-124-mediated lactate transporter (MCT1) inhibition

Primary research

LncRNA SNHG6 promotes chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in colorectal cancer cells

Primary research

HAND2-AS1 inhibits invasion and metastasis of cervical cancer cells via microRNA-330-5p-mediated LDOC1

Primary research

HOXB8 enhances the proliferation and metastasis of colorectal cancer cells by promoting EMT via STAT3 activation

Primary research

MicroRNA-96-3p promotes metastasis of papillary thyroid cancer through targeting SDHB
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits