nach oben

Erschienen in:

24.04.2018 | Preclinical study

Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness

verfasst von: Hidetaka Shima, Kumiko Kida, Shoko Adachi, Akimitsu Yamada, Sadatoshi Sugae, Kazutaka Narui, Yohei Miyagi, Mayuko Nishi, Akihide Ryo, Soichiro Murata, Hideki Taniguchi, Yasushi Ichikawa, Takashi Ishikawa, Itaru Endo

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Aldehyde dehydrogenase1 (ALDH1) is widely accepted as a stem cell marker for normal breast as well as in breast cancer. Although the clinical impact of ALDH1 was observed in our previous study, we do not know how ALDH1 affects stem cell features resulting in worsening of prognosis in breast cancer. The purpose of this study is to explore ALDH1-related gene and its function on cancer stem cell (CSC).

Methods

In five cases of ALDH1-positive triple-negative breast cancer, mRNA expression profile was compared between ALDH1-positive and ALDH1-negative cells by Affymetrix microarray analysis after microdissection. Among the genes modulated in ALDH1-positive cells, we focused on H19, which encodes a long non-coding RNA, in this study. An in-vitro study was conducted with H19 siRNA in HCC1934 and iCSCL10A cell lines. The association of H19 with prognosis was examined in 180 breast cancer cases.

Results

Network analysis revealed the existence of five genes related with H19, including miR-103, miR-107, let-7, miR-29b-1, and Trx. In-vitro analysis showed that suppression of H19 using siRNA reduces sphere formation capacity in both HCC1934 and iCSCL10A cell lines. In clinical studies, H19 expression was associated with hormone negativity, tumor size, and nodal status. Patients with H19 expression had significantly poor disease-free survival (DFS) (26.3 vs. 64.8% at 5 years, p = 0.001) and overall survival (OS) (28.9 vs. 68.3% at 5 years, p = 0.004). The effect of H19 expression on prognosis was the most significant in triple-negative breast cancer compared to that in other subtypes (20.0 vs. 65.4% at 5 years DFS, p = 0.012, 20.0 vs. 69.2% at 5 years OS, p = 0.016).

Conclusion

This study indicated that H19 was associated with stem cell phenotype in ALDH1-positive breast cancer. H19 regulates CSC and is associated with poor prognosis in breast cancer patients, particularly in triple-negative subtype.

Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM (2006) Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66(19):9339–9344. https://doi.org/10.1158/0008-5472.can-06-3126 CrossRefPubMed

Wang H, Zhang Y, Du Y (2013) Ovarian and breast cancer spheres are similar in transcriptomic features and sensitive to fenretinide. BioMed Res Int 2013:510905. https://doi.org/10.1155/2013/510905 PubMedPubMedCentralCrossRef

Shima H, Yamada A, Ishikawa T, Endo I (2017) Are breast cancer stem cells the key to resolving clinical issues in breast cancer therapy? Gland Surg 6(1):82–88. https://doi.org/10.21037/gs.2016.08.03 CrossRefPubMedPubMedCentral

Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111. https://doi.org/10.1038/35102167 CrossRefPubMed

Lehmann C, Jobs G, Thomas M, Burtscher H, Kubbies M (2012) Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells. Int J Oncol 41(6):1932–1942. https://doi.org/10.3892/ijo.2012.1654 CrossRefPubMedPubMedCentral

Ma I, Allan AL (2011) The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev 7(2):292–306. https://doi.org/10.1007/s12015-010-9208-4 CrossRefPubMed

Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA, Allan AL (2009) High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med 13(8b):2236–2252. https://doi.org/10.1111/j.1582-4934.2008.00455.x CrossRefPubMed

Kida K, Ishikawa T, Yamada A, Shimada K, Narui K, Sugae S, Shimizu D, Tanabe M, Sasaki T, Ichikawa Y, Endo I (2016) Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype. Breast Cancer Res Treat 156(2):261–269. https://doi.org/10.1007/s10549-016-3738-7 CrossRefPubMed

Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, Brown M, Viens P, Xerri L, Bertucci F, Stassi G, Dontu G, Birnbaum D, Wicha MS (2009) Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res 69(4):1302–1313. https://doi.org/10.1158/0008-5472.can-08-2741 CrossRefPubMedPubMedCentral

10.

Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, Cardenal F, Sanchez JM, Gumerlock PH, Taron M, Sanchez JJ, Danenberg KD, Danenberg PV, Rosell R (2002) Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Can Res 8(7):2286–2291

11.

Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic acids Res 31(4):e15CrossRefPubMedPubMedCentral

12.

Hubbell E, Liu WM, Mei R (2002) Robust estimators for expression analysis. Bioinformatics 18(12):1585–1592CrossRefPubMed

13.

Sato H, Ishida S, Toda K, Matsuda R, Hayashi Y, Shigetaka M, Fukuda M, Wakamatsu Y, Itai A (2005) New approaches to mechanism analysis for drug discovery using DNA microarray data combined with KeyMolnet. Curr Drug Discov Technol 2(2):89–98CrossRefPubMed

14.

Nishi M, Akutsu H, Kudoh A, Kimura H, Yamamoto N, Umezawa A, Lee SW, Ryo A (2014) Induced cancer stem-like cells as a model for biological screening and discovery of agents targeting phenotypic traits of cancer stem cell. Oncotarget 5(18):8665–8680. https://doi.org/10.18632/oncotarget.2356 CrossRefPubMedPubMedCentral

15.

Opdenaker LM, Modarai SR, Boman BM (2015) The proportion of ALDEFLUOR-positive cancer stem cells changes with cell culture density due to the expression of different ALDH isoforms. Cancer Stud Mol Med 2(2):87–95. https://doi.org/10.17140/csmmoj-2-113 CrossRefPubMedPubMedCentral

16.

Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, Cheang MC, Gelmon K, Nielsen TO, Blomqvist C, Heikkila P, Heikkinen T, Nevanlinna H, Akslen LA, Begin LR, Foulkes WD, Couch FJ, Wang X, Cafourek V, Olson JE, Baglietto L, Giles GG, Severi G, McLean CA, Southey MC, Rakha E, Green AR, Ellis IO, Sherman ME, Lissowska J, Anderson WF, Cox A, Cross SS, Reed MW, Provenzano E, Dawson SJ, Dunning AM, Humphreys M, Easton DF, Garcia-Closas M, Caldas C, Pharoah PD, Huntsman D (2010) Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med 7(5):e1000279. https://doi.org/10.1371/journal.pmed.1000279 CrossRefPubMedPubMedCentral

17.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502. https://doi.org/10.1001/jama.295.21.2492 CrossRefPubMed

18.

Liu Y, Lv DL, Duan JJ, Xu SL, Zhang JF, Yang XJ, Zhang X, Cui YH, Bian XW, Yu SC (2014) ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: a systematic review and meta-analysis. BMC Cancer 14:444. https://doi.org/10.1186/1471-2407-14-444 CrossRefPubMedPubMedCentral

19.

Wang JX, Zhang XJ, Li Q, Wang K, Wang Y, Jiao JQ, Feng C, Teng S, Zhou LY, Gong Y, Zhou ZX, Liu J, Wang JL, Li PF (2015) MicroRNA-103/107 regulate programmed necrosis and myocardial ischemia/reperfusion injury through targeting FADD. Circ Res 117(4):352–363. https://doi.org/10.1161/circresaha.117.305781 CrossRefPubMed

20.

Peng F, Li TT, Wang KL, Xiao GQ, Wang JH, Zhao HD, Kang ZJ, Fan WJ, Zhu LL, Li M, Cui B, Zheng FM, Wang HJ, Lam EW, Wang B, Xu J, Liu Q (2017) H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance. Cell Death Dis 8(1):e2569. https://doi.org/10.1038/cddis.2016.438 CrossRefPubMedPubMedCentral

21.

Tang Y, He R, An J, Deng P, Huang L, Yang W (2016) The effect of H19-miR-29b interaction on bleomycin-induced mouse model of idiopathic pulmonary fibrosis. Biochem Biophys Res Commun 479(3):417–423. https://doi.org/10.1016/j.bbrc.2016.09.028 CrossRefPubMed

22.

Lottin S, Vercoutter-Edouart AS, Adriaenssens E, Czeszak X, Lemoine J, Roudbaraki M, Coll J, Hondermarck H, Dugimont T, Curgy JJ (2002) Thioredoxin post-transcriptional regulation by H19 provides a new function to mRNA-like non-coding RNA. Oncogene 21(10):1625–1631. https://doi.org/10.1038/sj.onc.1205233 CrossRefPubMed

23.

Liu FT, Pan H, Xia GF, Qiu C, Zhu ZM (2016) Prognostic and clinicopathological significance of long noncoding RNA H19 overexpression in human solid tumors: evidence from a meta-analysis. Oncotarget 7(50):83177–83186. https://doi.org/10.18632/oncotarget.13076 PubMedPubMedCentralCrossRef

24.

Zemel S, Bartolomei MS, Tilghman SM (1992) Physical linkage of two mammalian imprinted genes, H19 and insulin-like growth factor 2. Nat Genet 2(1):61–65. https://doi.org/10.1038/ng0992-61 CrossRefPubMed

25.

Giannoukakis N, Deal C, Paquette J, Goodyer CG, Polychronakos C (1993) Parental genomic imprinting of the human IGF2 gene. Nat Genet 4(1):98–101. https://doi.org/10.1038/ng0593-98 CrossRefPubMed

26.

Zhang Y, Tycko B (1992) Monoallelic expression of the human H19 gene. Nat Genet 1(1):40–44. https://doi.org/10.1038/ng0492-40 CrossRefPubMed

27.

Wu T, Qu L, He G, Tian L, Li L, Zhou H, Jin Q, Ren J, Wang Y, Wang J, Kan X, Liu M, Shen J, Guo M, Sun Y (2016) Regulation of laryngeal squamous cell cancer progression by the lncRNA H19/miR-148a-3p/DNMT1 axis. Oncotarget 7(10):11553–11566. https://doi.org/10.18632/oncotarget.7270 PubMedPubMedCentralCrossRef

28.

Bauderlique-Le Roy H, Vennin C, Brocqueville G, Spruyt N, Adriaenssens E, Bourette RP (2015) Enrichment of human stem-like prostate cells with s-SHIP promoter activity uncovers a role in stemness for the long noncoding RNA H19. Stem Cells Dev 24(10):1252–1262. https://doi.org/10.1089/scd.2014.0386 CrossRefPubMedPubMedCentral

29.

Wang SH, Wu XC, Zhang MD, Weng MZ, Zhou D, Quan ZW (2016) Long noncoding RNA H19 contributes to gallbladder cancer cell proliferation by modulated miR-194-5p targeting AKT2. Tumour Biol 37(7):9721–9730. https://doi.org/10.1007/s13277-016-4852-1 CrossRefPubMed

30.

Chen JS, Wang YF, Zhang XQ, Lv JM, Li Y, Liu XX, Xu TP (2016) H19 serves as a diagnostic biomarker and up-regulation of H19 expression contributes to poor prognosis in patients with gastric cancer. Neoplasma 63(2):223–230. https://doi.org/10.4149/207_150821n454 PubMedCrossRef

31.

Yu LL, Chang K, Lu LS, Zhao D, Han J, Zheng YR, Yan YH, Yi P, Guo JX, Zhou YG, Chen M, Li L (2013) Lentivirus-mediated RNA interference targeting the H19 gene inhibits cell proliferation and apoptosis in human choriocarcinoma cell line JAR. BMC Cell Biol 14:26. https://doi.org/10.1186/1471-2121-14-26 CrossRefPubMedPubMedCentral

32.

Zeira E, Abramovitch R, Meir K, Even Ram S, Gil Y, Bulvik B, Bromberg Z, Levkovitch O, Nahmansson N, Adar R, Reubinoff B, Galun E, Gropp M (2015) The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells. Oncotarget 6(33):34691–34703. https://doi.org/10.18632/oncotarget.5787 CrossRefPubMedPubMedCentral

33.

Li W, Jiang P, Sun X, Xu S, Ma X, Zhan R (2016) Suppressing H19 modulates tumorigenicity and stemness in U251 and U87MG glioma cells. Cell Mol Neurobiol 36(8):1219–1227. https://doi.org/10.1007/s10571-015-0320-5 CrossRefPubMedPubMedCentral

34.

Yoshimizu T, Miroglio A, Ripoche MA, Gabory A, Vernucci M, Riccio A, Colnot S, Godard C, Terris B, Jammes H, Dandolo L (2008) The H19 locus acts in vivo as a tumor suppressor. Proc Natl Acad Sci USA 105(34):12417–12422. https://doi.org/10.1073/pnas.0801540105 CrossRefPubMedPubMedCentral

35.

Zhou W, Ye XL, Xu J, Cao MG, Fang ZY, Li LY, Guan GH, Liu Q, Qian YH, Xie D (2017) The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b. Sci Signal 10(483):eaak9557. https://doi.org/10.1126/scisignal.aak9557 CrossRefPubMed

36.

Polytarchou C, Iliopoulos D, Struhl K (2012) An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state. Proc Natl Acad Sci USA 109(36):14470–14475. https://doi.org/10.1073/pnas.1212811109 CrossRefPubMedPubMedCentral

37.

Drago-Ferrante R, Pentimalli F, Carlisi D, De Blasio A, Saliba C, Baldacchino S, Degaetano J, Debono J, Caruana-Dingli G, Grech G, Scerri C, Tesoriere G, Giordano A, Vento R, Di Fiore R (2017) Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation. Oncotarget 8(17):28939–28958. https://doi.org/10.18632/oncotarget.15960 CrossRefPubMedPubMedCentral

38.

Hansen JM, Go YM, Jones DP (2006) Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Ann Rev Pharmacol Toxicol 46:215–234. https://doi.org/10.1146/annurev.pharmtox.46.120604.141122 CrossRef

39.

Hill R, Wu H (2009) PTEN, stem cells, and cancer stem cells. J Biol Chem 284(18):11755–11759. https://doi.org/10.1074/jbc.R800071200 CrossRefPubMedPubMedCentral

Titel: Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness
verfasst von: Hidetaka Shima
Kumiko Kida
Shoko Adachi
Akimitsu Yamada
Sadatoshi Sugae
Kazutaka Narui
Yohei Miyagi
Mayuko Nishi
Akihide Ryo
Soichiro Murata
Hideki Taniguchi
Yasushi Ichikawa
Takashi Ishikawa
Itaru Endo
Publikationsdatum: 24.04.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4793-z

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness