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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Breast Cancer | Research

PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA

Authors: Liping Tan, Dongmei Mai, Bailin Zhang, Xiaobing Jiang, Jialiang Zhang, Ruihong Bai, Ying Ye, Mei Li, Ling Pan, Jiachun Su, Yanfen Zheng, Zexian Liu, Zhixiang Zuo, Qi Zhao, Xiaoxing Li, Xudong Huang, Jie Yang, Wen Tan, Jian Zheng, Dongxin Lin

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Background

Breast cancer is one of the most common malignancies and the major cause of cancer-related death in women. Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has been increasingly recognized, few studies have been explored the functional mechanism of piRNAs in breast cancer development and progression.

Methods

We examined the top 20 highly expressed piRNAs based on the analysis of TCGA breast cancer data in two patient cohorts to test the roles of piRNAs in breast cancer. The effects of piRNA-36,712 on the malignant phenotypes and chemosensitivity of breast cancer cells were detected in vitro and in vivo. MS2-RIP and reporter gene assays were conducted to identify the interaction and regulation among piRNA-36,712, miRNAs and SEPW1P. Kaplan-Meier estimate with log-rank test was used to compare patient survival by different piRNA-36,712 expression levels.

Results

We found piRNA-36,712 level was significantly lower in breast cancer than in normal breast tissues and low level was correlated with poor clinical outcome in patients. Functional studies demonstrated that piRNA-36,712 interacts with RNAs produced by SEPW1P, a retroprocessed pseudogene of SEPW1, and subsequently inhibits SEPW1 expression through competition of SEPW1 mRNA with SEPW1P RNA for microRNA-7 and microRNA-324. We also found that higher SEPW1 expression due to downregulation of piRNA-36,712 in breast cancer may suppress P53, leading to the upregulated Slug but decreased P21 and E-cadherin levels, thus promoting cancer cell proliferation, invasion and migration. Furthermore, we found that piRNA-36,712 had synergistic anticancer effects with the paclitaxel and doxorubicin, two chemotherapeutic agents for breast cancer.

Conclusions

These findings suggest that piRNA-36,712 is a novel tumor suppressor and may serve as a potential predictor for the prognosis of breast cancer patients.
Appendix
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Literature
1.
Ng KW, Anderson C, Marshall EA, Minatel BC, Enfield KS, Saprunoff HL, et al. Piwi-interacting RNAs in cancer: emerging functions and clinical utility. Mol Cancer. 2016;15:5.PubMedPubMedCentralCrossRef
2.
Girard A, Sachidanandam R, Hannon GJ, Carmell MA. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature. 2006;442(7099):199–202.PubMed
3.
Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD. A distinct small RNA pathway silences selfish genetic elements in the germline. Science. 2006;313(5785):320–4.PubMedCrossRef
4.
Xu M, You Y, Hunsicker P, Hori T, Small C, Griswold MD, et al. Mice deficient for a small cluster of Piwi-interacting RNAs implicate Piwi-interacting RNAs in transposon control. Biol Reprod. 2008;79(1):51–7.PubMedCrossRef
5.
Gou LT, Dai P, Yang JH, Xue Y, Hu YP, Zhou Y, et al. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Res. 2014;24(6):680–700.PubMedPubMedCentralCrossRef
6.
Martinez VD, Vucic EA, Thu KL, Hubaux R, Enfield KS, Pikor LA, et al. Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology. Sci Rep. 2015;5:10423.PubMedPubMedCentralCrossRef
7.
Yan Z, Hu HY, Jiang X, Maierhofer V, Neb E, He L, et al. Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res. 2011;39(15):6596–607.PubMedPubMedCentralCrossRef
8.
9.
Law PT, Qin H, Ching AK, Lai KP, Co NN, He M, et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma. J Hepatol. 2013;58(6):1165–73.PubMedCrossRef
10.
Muller S, Raulefs S, Bruns P, Afonso-Grunz F, Plotner A, Thermann R, et al. Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol Cancer. 2015;14:94.PubMedPubMedCentralCrossRef
11.
Martinez VD, Enfield KS, Rowbotham DA, Lam WL. An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for identifying signatures of gastric cancer recurrence. Gastric cancer. 2016;19(2):660–5.PubMedCrossRef
12.
Fu A, Jacobs DI, Hoffman AE, Zheng T, Zhu Y. PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome. Carcinogenesis. 2015;36(10):1094–102.PubMedPubMedCentralCrossRef
13.
Yan H, Wu QL, Sun CY, Ai LS, Deng J, Zhang L, et al. piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia. 2015;29(1):196–206.PubMedCrossRef
14.
Chu H, Hui G, Yuan L, Shi D, Wang Y, Du M, et al. Identification of novel piRNAs in bladder cancer. Cancer Lett. 2015;356(2 Pt B):561–7.PubMedCrossRef
15.
Yin J, Jiang XY, Qi W, Ji CG, Xie XL, Zhang DX, et al. piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1. Cancer Sci. 2017;108(9):1746–56.PubMedPubMedCentralCrossRef
16.
Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, et al. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett. 2012;315(1):12–7.PubMedCrossRef
17.
Cui L, Lou Y, Zhang X, Zhou H, Deng H, Song H, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem. 2011;44(13):1050–7.PubMedCrossRef
18.
Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011;378(9801):1461–84.PubMedCrossRef
19.
Van't Veer LJ, Dai H, Van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRef
20.
Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell. 2006;10(6):529–41.PubMedCrossRef
21.
Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK, et al. Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet. 2008;82(4):937–48.PubMedPubMedCentralCrossRef
22.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.PubMedCrossRef
23.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.PubMedPubMedCentralCrossRef
24.
Podo F, Buydens LM, Degani H, Hilhorst R, Klipp E, Gribbestad IS, et al. Triple-negative breast cancer: present challenges and new perspectives. Mol Oncol. 2010;4(3):209–29.PubMedPubMedCentralCrossRef
25.
Patsialou A, Wang Y, Lin J, Whitney K, Goswami S, Kenny PA, et al. Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients. Breast Cancer Res. 2012;14(5):R139.PubMedPubMedCentralCrossRef
26.
Van de Vijver MJ, He YD, Van't Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.PubMedCrossRef
27.
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.PubMedCrossRef
28.
Dowsett M, Cuzick J, Wale C, Forbes J, Mallon EA, Salter J, et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol. 2010;28(11):1829–34.PubMedCrossRef
29.
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast Cancer. N Engl J Med. 2018;379(2):111–21.PubMedCrossRef
30.
Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55–65.PubMedCrossRef
31.
Zhang P, Kang JY, Gou LT, Wang J, Xue Y, Skogerboe G, et al. MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes. Cell Res. 2015;25(2):193–207.PubMedPubMedCentralCrossRef
32.
Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002;21(25):3988–99.PubMedCrossRef
33.
Deng W, Lin H. Miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell. 2002;2(6):819–30.PubMedCrossRef
34.
Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465(7301):1033–8.PubMedPubMedCentralCrossRef
35.
Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Leopold V, et al. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell. 2015;161(2):319–32.PubMedCrossRef
36.
Hawkes WC, Alkan Z. Delayed cell cycle progression in selenoprotein W-depleted cells is regulated by a mitogen-activated protein kinase kinase 4-p38/c-Jun NH2-terminal kinase-p53 pathway. J Biol Chem. 2012;287(33):27371–9.PubMedPubMedCentralCrossRef
37.
Hawkes WC, Printsev I, Alkan Z. Selenoprotein W depletion induces a p53- and p21-dependent delay in cell cycle progression in RWPE-1 prostate epithelial cells. J Cell Biochem. 2012;113(1):61–9.PubMedCrossRef
38.
Wang SP, Wang WL, Chang YL, Wu CT, Chao YC, Kao SH, et al. p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of slug. Nat Cell Biol. 2009;11(6):694–704.PubMedCrossRef
39.
Hajra KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res. 2002;62(6):1613–8.PubMed
40.
Cristofanilli M, Gonzalez-Angulo AM, Buzdar AU, Kau SW, Frye DK, Hortobagyi GN. Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: the M. D. Anderson Cancer center experience. Clin Breast Cancer. 2004;4(6):415–9.PubMedCrossRef
41.
Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005;23(16):3686–96.PubMedCrossRef
42.
Fan W. Possible mechanisms of paclitaxel-induced apoptosis. Biochem Pharmacol. 1999;57(11):1215–21.PubMedCrossRef
43.
Siddiqi S, Matushansky I. Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem. 2012;113(2):373–80.PubMedCrossRef
44.
He X, Chen X, Zhang X, Duan X, Pan T, Hu Q, et al. An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes. Nucleic Acids Res. 2015;43(7):3712–25.PubMedPubMedCentralCrossRef
45.
Mei Y, Wang Y, Kumari P, Shetty AC, Clark D, Gable T, et al. A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells. Nat Commun. 2015;6:7316.PubMedPubMedCentralCrossRef
46.
Zhong F, Zhou N, Wu K, Guo Y, Tan W, Zhang H, et al. A SnoRNA-derived piRNA interacts with human interleukin-4 pre-mRNA and induces its decay in nuclear exosomes. Nucleic Acids Res. 2015;43(21):10474–91.PubMedPubMedCentral
47.
48.
49.
Jeong D, Kim TS, Chung YW, Lee BJ, Kim IY. Selenoprotein W is a glutathione-dependent antioxidant in vivo. FEBS Lett. 2002;517(1–3):225–8.PubMedCrossRef
50.
Guariniello S, Di Bernardo G, Colonna G, Cammarota M, Castello G, Costantini S. Evaluation of the selenotranscriptome expression in two hepatocellular carcinoma cell lines. Anal Cell Pathol (Amst) 2015;2015:419561.
51.
52.
Wu HC, Southey MC, Hibshoosh H, Santella RM, Terry MB. DNA methylation in breast tumor from high-risk women in the breast Cancer family registry. Anticancer Res. 2017;37(2):659–64.PubMedPubMedCentralCrossRef
53.
Hawkes WC, Wang TT, Alkan Z, Richter BD, Dawson K. Selenoprotein W modulates control of cell cycle entry. Biol Trace Elem Res. 2009;131(3):229–44.PubMedCrossRef
54.
55.
Shih JY, Tsai MF, Chang TH, Chang YL, Yuan A, Yu CJ, et al. Transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma. Clin Cancer Res. 2005;11(22):8070–8.PubMedCrossRef
56.
Shioiri M, Shida T, Koda K, Oda K, Seike K, Nishimura M, et al. Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Br J Cancer. 2006;94(12):1816–22.PubMedPubMedCentralCrossRef
57.
Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12(6):488–96.PubMedCrossRef
58.
Walerych D, Napoli M, Collavin L, Del Sal G. The rebel angel: mutant p53 as the driving oncogene in breast cancer. Carcinogenesis. 2012;33(11):2007–17.PubMedPubMedCentralCrossRef
59.
Joo JH, Kim SS, Son BH, S DOA, Jung JH, Choi EK, et al. Evaluation of the prognostic stage in the 8th edition of the American joint committee on Cancer in patients with breast Cancer and internal mammary lymph node metastasis. Anticancer Res. 2018;38(9):5357–61.PubMedCrossRef
60.
Sax JK, Fei P, Murphy ME, Bernhard E, Korsmeyer SJ, El-Deiry WS. BID regulation by p53 contributes to chemosensitivity. Nat Cell Biol. 2002;4(11):842–9.PubMedCrossRef
61.
Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087–106.PubMedCrossRef
Metadata
Title
PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA
Authors
Liping Tan
Dongmei Mai
Bailin Zhang
Xiaobing Jiang
Jialiang Zhang
Ruihong Bai
Ying Ye
Mei Li
Ling Pan
Jiachun Su
Yanfen Zheng
Zexian Liu
Zhixiang Zuo
Qi Zhao
Xiaoxing Li
Xudong Huang
Jie Yang
Wen Tan
Jian Zheng
Dongxin Lin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-0940-3

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