Identification of PIWI-interacting RNA modules by weighted correlation network analysis
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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.
KeywordsWGCNA PiRNA module Cancer
This work was supported by the Natural Science Foundation of China under Grants 61571341, 61201312 and 91530113, Research Fund for the Doctoral Program of Higher Education of China (No. 2013 0203110017), the Fundamental Research Funds for the Central Universities of China (Nos BDY171416, JBZ170301, JB140306 and 20101164977), the Natural Science Foundation of Shaanxi Province in China (2015JM6275, 2017JM6024).
Author contributions Yajun Liu and Junying Zhang participated in the design of the study and drafted the manuscript. Yajun Liu conducted the data analysis. Aimin Li, Yuanyuan Zhang, and Yaoyao Li proposed numerous constructive ideas and revised the manuscript in detail. In addition, Xiguo Yuan, Zhongzhen He, Zhaowen Liu, and Shouheng Tuo contributed some insights into this work.
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Conflicts of interest
The authors declare that they have no conflicts of interest with respect to the publication of this paper.
- 5.Zhang, B., Horvath, S.: A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol. 4 (2005). Article 17Google Scholar
- 7.Vinolas, N., Aya, F., Navarro, A., Marrades, R.M., Cordeiro, A., Fernandez, A., Chic, N., Gimferrer, J.M., Ramirez, J., Molins, L et al.: piRNA-651 as a prognostic marker in surgically resected non-small-cell lung cancer. J. Clin. Oncol. 33(15), 11043 (2015)Google Scholar
- 11.Li, Y., Wu, X., Gao, H., Jin, J., Li, A., Kim, Y., Wang, F., Wang, J., Nelson, R., Mu, B., et al.: piR-32052, PiR-39894 and PiR-43607, three novel dicer-independent Piwi-interacting RNAs derived from the same PiRNA cluster, are up-regulated in metastatic renal cell carcinoma. Modern Pathol. 27, 244a–244a (2014)Google Scholar
- 12.Busch, J., Ralla, B., Jung, M., Wotschofsky, Z., Trujillo-Arribas, E., Schwabe, P., Kilic, E., Fendler, A., Jung, K.: Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas. J. Exp. Clin. Cancer Res. 34(1), 61 (2015)Google Scholar
- 16.Rizzo, F., Rinaldi, A., Marchese, G., Coviello, E., Sellitto, A., Cordella, A., Giurato, G., Nassa, G., Ravo, M., Tarallo, R., et al.: Specific patterns of PIWI-interacting small noncoding RNA expression in dysplastic liver nodules and hepatocellular carcinoma. Oncotarget 7(34), 54650–54661 (2016)CrossRefGoogle Scholar
- 19.Pretty, R.: WGCNA-package WGCNA weighted gene co-expression network analysis. BMC Bioinform. 9(1), 559 (2011)Google Scholar
- 25.Byers, T., Wender, R.C., Jemal, A., Baskies, A.M., Ward, E.E., Brawley, O.W.: The American Cancer Society challenge goal to reduce US cancer mortality by 50% between 1990 and 2015: results and reflections. CA 66(5), 359 (2016)Google Scholar
- 26.Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., Jemal, A., Yu, X.Q., He, J.: Cancer statistics in China, 2015. CA 66(2), 115 (2016)Google Scholar