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
Tumor Biology
Published in: Tumor Biology 1/2016

01-01-2016 | Original Article

AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis

Authors: Zhaoyang Zeng, Hao Bo, Zhaojian Gong, Yu Lian, Xiayu Li, Xiaoling Li, Wenling Zhang, Hao Deng, Ming Zhou, Shuping Peng, Guiyuan Li, Wei Xiong

Published in: Tumor Biology | Issue 1/2016

Login to get access

Abstract

Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cancer. Significant fraction of lncRNAs is represented on widely used microarray platforms; however, many of which have no known function. To discover novel lung cancer-related lncRNAs, we analyzed the lncRNA expression patterns in five sets of previously published lung cancer gene expression profile data that were represented on Affymetrix HG-U133 Plus 2.0 array, and identified dysregulated lncRNAs in lung cancer. One lncRNA, actin filament associated protein 1 antisense RNA1 (AFAP1-AS1), was the most significantly upregulated in lung cancer and associated with poor prognosis. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the cell invasive and migration capability in lung cancer cells. AFAP1-AS1 knockdown also increased the expression of its antisense protein coding gene, actin filament associated protein 1 (AFAP1), and affected the expression levels of several small GTPase family members and molecules in the actin cytokeratin signaling pathway, which suggested that AFAP1-AS1 promoted cancer cell metastasis via regulation of actin filament integrity. Our findings extend the number of noncoding RNAs functionally implicated in lung cancer progression and highlight the role of AFAP1-AS1 as potential prognostic biomarker and therapeutic target of lung cancer.
Literature
1.
2.
Wang M, Cao JX, Pan JH, Liu YS, Xu BL, et al. Adoptive immunotherapy of cytokine-induced killer cell therapy in the treatment of non-small cell lung cancer. PLoS One. 2014;9:e112662.CrossRefPubMedPubMedCentral
3.
Zhang NN, Liu YT, Ma L, Wang L, Hao XZ, et al. The molecular detection and clinical significance of ALK rearrangement in selected advanced non-small cell lung cancer: ALK expression provides insights into ALK targeted therapy. PLoS One. 2014;9:e84501.CrossRefPubMedPubMedCentral
4.
Aggarwal C. Targeted therapy for lung cancer: present and future. Ann Palliat Med. 2014;3:229–35.PubMed
5.
Lu JY, Zhang M, Jin HL, Zhu JL, Wei JL, et al. Advances on molecular mechanism of chronic inflammation-driven lung cancer induced by environmental carcinogens. Prog Biochem Biophys. 2014;41:41–51.
6.
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.CrossRefPubMed
7.
Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15:7–21.CrossRefPubMed
8.
9.
Gong Z, Zhang S, Zhang W, Huang H, Li Q, et al. Long non-coding RNAs in cancer. Sci China Life Sci. 2012;55:1120–4.CrossRefPubMed
10.
Gong Z, Zhang S, Zeng Z, Wu H, Yang Q, et al. LOC401317, a p53-regulated long non-coding RNA, inhibits cell proliferation and induces apoptosis in the nasopharyngeal carcinoma cell line HNE2. PLoS One. 2014;9:e110674.CrossRefPubMedPubMedCentral
11.
Ono H, Motoi N, Nagano H, Miyauchi E, Ushijima M, et al. Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer. Cancer Med. 2014;3:632–42.CrossRefPubMedPubMedCentral
12.
Zhao W, An Y, Liang Y, Xie XW. Role of HOTAIR long noncoding RNA in metastatic progression of lung cancer. Eur Rev Med Pharmacol Sci. 2014;18:1930–6.PubMed
13.
Matouk IJ, Halle D, Gilon M, Hochberg A. The non-coding RNAs of the H19-IGF2 imprinted loci: a focus on biological roles and therapeutic potential in Lung Cancer. J Transl Med. 2015;13:113.CrossRefPubMedPubMedCentral
14.
Lin L, Gu ZT, Chen WH, Cao KJ. Increased expression of the long non-coding RNA ANRIL promotes lung cancer cell metastasis and correlates with poor prognosis. Diagn Pathol. 2015;10:14.CrossRefPubMedPubMedCentral
15.
Shen L, Chen L, Wang Y, Jiang X, Xia H, et al. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. J Neurooncol. 2015;121:101–8.CrossRefPubMed
16.
Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73:1180–9.CrossRefPubMed
17.
Weber DG, Johnen G, Casjens S, Bryk O, Pesch B, et al. Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes. 2013;6:518.CrossRefPubMedPubMedCentral
18.
Dong S, Qu X, Li W, Zhong X, Li P, et al. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol. 2015;8:43.CrossRefPubMedPubMedCentral
19.
Shi X, Sun M, Liu H, Yao Y, Kong R, et al. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2015;54 Suppl 1:E1–E12.CrossRefPubMed
20.
Okayama H, Kohno T, Ishii Y, Shimada Y, Shiraishi K, et al. Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res. 2012;72:100–11.CrossRefPubMed
21.
Lu TP, Tsai MH, Lee JM, Hsu CP, Chen PC, et al. Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women. Cancer Epidemiol Biomarkers Prev. 2010;19:2590–7.CrossRefPubMed
22.
Wei TY, Hsia JY, Chiu SC, Su LJ, Juan CC, et al. Methylosome protein 50 promotes androgen- and estrogen-independent tumorigenesis. Cell Signal. 2014;26:2940–50.CrossRefPubMed
23.
Sanchez-Palencia A, Gomez-Morales M, Gomez-Capilla JA, Pedraza V, Boyero L, et al. Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer. Int J Cancer. 2011;129:355–64.CrossRefPubMed
24.
Botling J, Edlund K, Lohr M, Hellwig B, Holmberg L, et al. Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation. Clin Cancer Res. 2013;19:194–204.CrossRefPubMed
25.
Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001;98:5116–21.CrossRefPubMedPubMedCentral
26.
Zeng Z, Zhou Y, Xiong W, Luo X, Zhang W, et al. Analysis of gene expression identifies candidate molecular markers in nasopharyngeal carcinoma using microdissection and cDNA microarray. J Cancer Res Clin Oncol. 2007;133:71–81.CrossRefPubMed
27.
Liao Q, Zeng Z, Guo X, Li X, Wei F, et al. LPLUNC1 suppresses IL-6-induced nasopharyngeal carcinoma cell proliferation via inhibiting the Stat3 activation. Oncogene. 2014;33:2098–109.CrossRefPubMed
28.
Yang Y, Liao Q, Wei F, Li X, Zhang W, et al. LPLUNC1 inhibits nasopharyngeal carcinoma cell growth via down-regulation of the MAP kinase and cyclin D1/E2F pathways. PLoS One. 2013;8:e62869.CrossRefPubMedPubMedCentral
29.
Xiong W, Wu X, Starnes S, Johnson SK, Haessler J, et al. An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma. Blood. 2008;112:4235–46.CrossRefPubMedPubMedCentral
30.
Dorfleutner A, Cho Y, Vincent D, Cunnick J, Lin H, et al. Phosphorylation of AFAP-110 affects podosome lifespan in A7r5 cells. J Cell Sci. 2008;121:2394–405.CrossRefPubMed
31.
Walker VG, Ammer A, Cao Z, Clump AC, Jiang BH, et al. PI3K activation is required for PMA-directed activation of cSrc by AFAP-110. Am J Physiol Cell Physiol. 2007;293:C119–32.CrossRefPubMed
32.
Qian Y, Gatesman AS, Baisden JM, Zot HG, Cherezova L, et al. Analysis of the role of the leucine zipper motif in regulating the ability of AFAP-110 to alter actin filament integrity. J Cell Biochem. 2004;91:602–20.CrossRefPubMed
33.
Ambriz-Pena X, Garcia-Zepeda EA, Meza I, Soldevila G. Jak3 enables chemokine-dependent actin cytoskeleton reorganization by regulating cofilin and Rac/Rhoa GTPases activation. PLoS One. 2014;9:e88014.CrossRefPubMedPubMedCentral
34.
Sit ST, Manser E. Rho GTPases and their role in organizing the actin cytoskeleton. J Cell Sci. 2011;124:679–83.CrossRefPubMed
35.
Yang Y, Li H, Hou S, Hu B, Liu J, et al. The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 2013;8:e65309.CrossRefPubMedPubMedCentral
36.
Yang X, Gao L, Guo X, Shi X, Wu H, et al. A network based method for analysis of lncRNA-disease associations and prediction of lncRNAs implicated in diseases. PLoS One. 2014;9:e87797.CrossRefPubMedPubMedCentral
37.
Negishi M, Wongpalee SP, Sarkar S, Park J, Lee KY, et al. A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. PLoS One. 2014;9:e95216.CrossRefPubMedPubMedCentral
38.
Li YW, Wang YM, Zhang XY, Xue D, Kuang B, et al. Progress of long noncoding RNA HOTAIR in human cancer. Progress in Biochemistry and Biophysics. 2015;42:228–35.
39.
Tang K, Wei F, Bo H, Huang HB, Zhang WL, et al. Cloning and functional characterization of a novel long non-coding RNA gene associated with hepatocellular carcinoma. Prog Biochem Biophys. 2014;41:153–62.
40.
Zhang W, Fan S, Zou G, Shi L, Zeng Z, et al. Lactotransferrin could be a novel independent molecular prognosticator of nasopharyngeal carcinoma. Tumour Biol. 2015;36:675–83.CrossRefPubMed
41.
Zhang HM, Yang FQ, Chen SJ, Che J, Zheng JH. Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol. 2015;36:2947–55.CrossRefPubMed
42.
Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9:e1003368.CrossRefPubMedPubMedCentral
43.
Pang EJ, Yang R, Fu XB, Liu YF. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. 2015;36:2403–7.CrossRefPubMed
44.
Ma KX, Wang HJ, Li XR, Li T, Su G, et al. Long noncoding RNA MALAT1 associates with the malignant status and poor prognosis in glioma. Tumour Biol. 2015;36:3355–9.CrossRefPubMed
45.
Ji Q, Liu X, Fu X, Zhang L, Sui H, et al. Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/beta-catenin signal pathway. PLoS One. 2013;8:e78700.CrossRefPubMedPubMedCentral
46.
Dong Y, Liang G, Yuan B, Yang C, Gao R, et al. MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol. 2015;36:1477–86.CrossRefPubMed
47.
Guan Y, Kuo WL, Stilwell JL, Takano H, Lapuk AV, et al. Amplification of PVT1 contributes to the pathophysiology of ovarian and breast cancer. Clin Cancer Res. 2007;13:5745–55.CrossRefPubMed
48.
Kong R, Zhang EB, Yin DD, You LH, Xu TP, et al. Long noncoding RNA PVT1 indicates a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically regulating p15 and p16. Mol Cancer. 2015;14:82.CrossRefPubMedPubMedCentral
49.
Wang F, Yuan JH, Wang SB, Yang F, Yuan SX, et al. Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatology. 2014;60:1278–90.CrossRefPubMed
50.
Zhang W, Huang C, Gong Z, Zhao Y, Tang K, et al. Expression of LINC00312, a long intergenic non-coding RNA, is negatively correlated with tumor size but positively correlated with lymph node metastasis in nasopharyngeal carcinoma. J Mol Histol. 2013;44:545–54.CrossRefPubMed
51.
Wu W, Bhagat TD, Yang X, Song JH, Cheng Y, et al. Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2013;144(956–966):e954.
52.
Yuan SX, Tao QF, Wang J, Yang F, Liu L, et al. Antisense long non-coding RNA PCNA-AS1 promotes tumor growth by regulating proliferating cell nuclear antigen in hepatocellular carcinoma. Cancer Lett. 2014;349:87–94.CrossRefPubMed
53.
Sehgal L, Mathur R, Braun FK, Wise JF, Berkova Z, et al. FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma. Leukemia. 2014;28:2376–87.CrossRefPubMed
54.
Baisden JM, Gatesman AS, Cherezova L, Jiang BH, Flynn DC. The intrinsic ability of AFAP-110 to alter actin filament integrity is linked with its ability to also activate cellular tyrosine kinases. Oncogene. 2001;20:6607–16.CrossRefPubMed
55.
Baisden JM, Qian Y, Zot HM, Flynn DC. The actin filament-associated protein AFAP-110 is an adaptor protein that modulates changes in actin filament integrity. Oncogene. 2001;20:6435–47.CrossRefPubMed
56.
Dorfleutner A, Stehlik C, Zhang J, Gallick GE, Flynn DC. AFAP-110 is required for actin stress fiber formation and cell adhesion in MDA-MB-231 breast cancer cells. J Cell Physiol. 2007;213:740–9.CrossRefPubMed
57.
Zhang J, Park SI, Artime MC, Summy JM, Shah AN, et al. AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts. J Clin Invest. 2007;117:2962–73.CrossRefPubMedPubMedCentral
Metadata
Title
AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis
Authors
Zhaoyang Zeng
Hao Bo
Zhaojian Gong
Yu Lian
Xiayu Li
Xiaoling Li
Wenling Zhang
Hao Deng
Ming Zhou
Shuping Peng
Guiyuan Li
Wei Xiong
Publication date
01-01-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3860-x

Other articles of this Issue 1/2016

Tumor Biology 1/2016 Go to the issue

Original Article

Long noncoding RNA NEAT1 promotes glioma pathogenesis by regulating miR-449b-5p/c-Met axis

Original Article

MiR-375 targets KLF4 and impacts the proliferation of colorectal carcinoma

Original Article

Staphylococcal enterotoxin B/texosomes as a candidate for breast cancer immunotherapy

Research Article

The role of stearoyl-coenzyme A desaturase 1 in clear cell renal cell carcinoma

Review

MicroRNAs, TGF-β signaling, and the inflammatory microenvironment in cancer

Original Article

Delivery of miR-155 to retinal pigment epithelial cells mediated by Burkitt’s lymphoma exosomes
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