Identification of PIWI-interacting RNA modules by weighted correlation network analysis

PIWI-interacting RNAs (piRNAs) are the largest class of small noncoding RNAs in animal cells; they cooperate with PIWI proteins to safeguard the genome. Although several studies have established that piRNAs can be biomarkers of cancer, it is still difficult to elucidate the exact function of piRNAs. In addition, researchers need to further investigate the interplay between piRNAs and piRNA groups in tumorigenesis. To identify cancer-associated piRNA-modules, we performed a weighted gene coexpression network analysis (WGCNA) on piRNA expression data from 11 types of cancer. Thereafter, genes associated with hub piRNAs in modules were predicted, and functional analysis of these genes was used to interpret the relation between piRNA and cancer. The results indicated that these piRNA modules have significant associations with cancer. A module with a high correlation coefficient (cor: −0.83, p value: 1.86E−128) was found; it was especially relevant to head and neck squamous cell carcinoma. Moreover, we found that hub piRNAs in modules may contribute to metastasis. This finding advances the understanding of piRNA function and its association with human cancer.

[1]  Jing Wang,et al.  WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013 , 2013, Nucleic Acids Res..

[2]  A. Jemal,et al.  The American Cancer Society challenge goal to reduce US cancer mortality by 50% between 1990 and 2015: Results and reflections , 2016, CA: a cancer journal for clinicians.

[3]  Zhen Jiang,et al.  piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. , 2011, Clinica chimica acta; international journal of clinical chemistry.

[4]  W. Lam,et al.  HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer. , 2016, Oral oncology.

[5]  Xiaohong Lv,et al.  piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling , 2016, Tumor Biology.

[6]  A. Jemal,et al.  Cancer statistics in China, 2015 , 2016, CA: a cancer journal for clinicians.

[7]  Steve Horvath,et al.  WGCNA: an R package for weighted correlation network analysis , 2008, BMC Bioinformatics.

[8]  V. Kim,et al.  Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. , 2006, Genes & development.

[9]  Bing Zhang,et al.  WebGestalt: an integrated system for exploring gene sets in various biological contexts , 2005, Nucleic Acids Res..

[10]  Cai-Xia Yang,et al.  Small RNA regulation of reproductive function , 2014, Molecular reproduction and development.

[11]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[12]  Luciano Milanesi,et al.  Specific patterns of PIWI-interacting small noncoding RNA expression in dysplastic liver nodules and hepatocellular carcinoma , 2016, Oncotarget.

[13]  Sambasivarao Damaraju,et al.  Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer , 2016, Oncotarget.

[14]  K. Jung,et al.  Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas , 2015, Journal of experimental & clinical cancer research : CR.

[15]  Chao Qin,et al.  Identification of novel piRNAs in bladder cancer. , 2015, Cancer letters.

[16]  K. Wang,et al.  piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma , 2014, Leukemia.

[17]  W. Lam,et al.  An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for identifying signatures of gastric cancer recurrence , 2016, Gastric Cancer.

[18]  Dan Li,et al.  piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4. , 2016, International journal of molecular medicine.

[19]  S. Horvath,et al.  Statistical Applications in Genetics and Molecular Biology , 2011 .

[20]  Jia Cheng,et al.  piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. , 2012, Cancer letters.

[21]  Emily A. Vucic,et al.  Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology , 2015, Scientific Reports.

[22]  Jef D. Boeke,et al.  Mighty Piwis Defend the Germline against Genome Intruders , 2007, Cell.

[23]  H. Zhang,et al.  The expression of stem cell protein Piwil2 and piR-932 in breast cancer. , 2013, Surgical oncology.

[24]  Michael Schroeder,et al.  GoPubMed: exploring PubMed with the Gene Ontology , 2005, Nucleic Acids Res..