The pseudogene-derived long noncoding RNA SFTA1P is down-regulated and suppresses cell migration and invasion in lung adenocarcinoma

Pseudogenes were once considered to be genomic fossils without biological function. Interestingly, recent evidence showed that a lot of pseudogenes are transcribed in human cancers, and their alterations contribute to multiple cancer development and progression. It is apparent that many pseudogenes transcribe noncoding RNAs and contribute to the role noncoding genome plays in human cancers. On this basis, some pseudogene transcripts are currently ranked among the classes of long noncoding RNAs. In this study, we identified a new pseudogene-derived long noncoding RNA termed SFTA1P by analyzing the microarray data of non–small cell lung cancer from Gene Expression Omnibus datasets. We found that SFTA1P expression was significantly decreased in non–small cell lung cancer tissues compared with normal tissues in non–small cell lung cancer microarray data. Moreover, decreased SFTA1P expression is only correlated with lung adenocarcinoma patients’ poor survival time but not with lung squamous cell carcinoma patients’ survival. In addition, gain-of-function studies including growth curves, migration, invasion assays, and in vivo studies were performed to verify the tumor suppressor role of SFTA1P in non–small cell lung cancer. Finally, the potential underlying pathways involved in SFTA1P were investigated by analyzing the SFTA1P-correlated genes in The Cancer Genome Atlas lung adenocarcinoma and normal tissues RNA sequencing data. Taken together, these findings demonstrate that pseudogene-derived long noncoding RNA SFTA1P exerts the tumor suppressor functions in human lung adenocarcinoma. Our investigation reveals the novel roles of pseudogene in lung adenocarcinoma, which may serve as a new target for lung adenocarcinoma diagnosis and therapy.

[1]  Xiaoqiang Guo,et al.  Pseudogene PTENP1 Suppresses Gastric Cancer Progression by Modulating PTEN. , 2016, Anti-cancer agents in medicinal chemistry.

[2]  Xuefei Shi,et al.  Pseudogene-expressed RNAs: a new frontier in cancers , 2016, Tumor Biology.

[3]  Huafeng Xie,et al.  Polycomb Repressive Complex 2 Is a Barrier to KRAS-Driven Inflammation and Epithelial-Mesenchymal Transition in Non-Small-Cell Lung Cancer. , 2016, Cancer cell.

[4]  Tzong-Ming Shieh,et al.  Long non-coding RNA AOC4P suppresses hepatocellular carcinoma metastasis by enhancing vimentin degradation and inhibiting epithelial-mesenchymal transition , 2015, Oncotarget.

[5]  Thomas M. Keane,et al.  The BRAF Pseudogene Functions as a Competitive Endogenous RNA and Induces Lymphoma In Vivo , 2015, Cell.

[6]  M. Pacyna‐Gengelbach,et al.  HOPX is methylated and exerts tumour‐suppressive function through Ras‐induced senescence in human lung cancer , 2015, The Journal of pathology.

[7]  I. Goodhead,et al.  Taking the pseudo out of pseudogenes. , 2015, Current opinion in microbiology.

[8]  Dawei Li,et al.  FOXM1 Promotes Lung Adenocarcinoma Invasion and Metastasis by Upregulating SNAIL , 2015, International journal of biological sciences.

[9]  Jiancheng Luo,et al.  Comprehensive characterization of cancer subtype associated long non-coding RNAs and their clinical implications , 2014, Scientific Reports.

[10]  Qihong Huang,et al.  Pseudogene PTENP1 Functions as a Competing Endogenous RNA to Suppress Clear-Cell Renal Cell Carcinoma Progression , 2014, Molecular Cancer Therapeutics.

[11]  H. Kazazian Processed pseudogene insertions in somatic cells , 2014, Mobile DNA.

[12]  R. Verhaak,et al.  The Pan-Cancer Analysis of Pseudogene Expression Reveals Biologically and Clinically Relevant Tumour Subtypes , 2014, Nature Communications.

[13]  Sandra A O'Toole,et al.  Molecular biology of lung cancer. , 2013, Journal of thoracic disease.

[14]  Xiu-Jie Wang,et al.  Pseudogenes: pseudo or real functional elements? , 2013, Journal of genetics and genomics = Yi chuan xue bao.

[15]  K. Morris,et al.  A pseudogene long noncoding RNA network regulates PTEN transcription and translation in human cells , 2013, Nature Structural &Molecular Biology.

[16]  A. Jemal,et al.  Cancer statistics, 2013 , 2013, CA: a cancer journal for clinicians.

[17]  M. Gerstein,et al.  The GENCODE pseudogene resource , 2012, Genome Biology.

[18]  Bronwen L. Aken,et al.  GENCODE: The reference human genome annotation for The ENCODE Project , 2012, Genome research.

[19]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[20]  Raymond K. Auerbach,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[21]  S. Dhanasekaran,et al.  Expressed Pseudogenes in the Transcriptional Landscape of Human Cancers , 2012, Cell.

[22]  Ferdinando Di Cunto,et al.  Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs , 2011, Cell.

[23]  A. Jemal,et al.  Cancer statistics, 2011 , 2011, CA: a cancer journal for clinicians.

[24]  E. Punch,et al.  Pseudogenes: pseudo-functional or key regulators in health and disease? , 2011, RNA.

[25]  P. Fraser,et al.  No-Nonsense Functions for Long Noncoding RNAs , 2011, Cell.

[26]  Kenneth S Kosik,et al.  MicroRNAs and Cellular Phenotypy , 2010, Cell.

[27]  Xiaoguang Fang,et al.  MicroRNAs: novel regulators in the hallmarks of human cancer. , 2009, Cancer letters.

[28]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[29]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[30]  P. Johnsson,et al.  Pseudogene-Expressed RNAs: Emerging Roles in Gene Regulation and Disease. , 2016, Current topics in microbiology and immunology.

[31]  Renato Martins,et al.  Non-small cell lung cancer. , 2012, Journal of the National Comprehensive Cancer Network : JNCCN.

[32]  A. Jemal,et al.  Global Cancer Statistics , 2011 .