Skip to main content
Erschienen in: Tumor Biology 12/2016

30.11.2016 | Original Article

LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes

verfasst von: Jin Yan, Yini Dang, Shiyu Liu, Yifeng Zhang, Guoxin Zhang

Erschienen in: Tumor Biology | Ausgabe 12/2016

Einloggen, um Zugang zu erhalten

Abstract

Altered expression of long noncoding RNAs (lncRNAs) has shown to associate with human cancer development and progression and drug resistance. LncRNA HOX antisense intergenic RNA (HOTAIR) regulates chromatin state and highly expressed in various human cancers. This study analyzed HOTAIR expression in gastric cancer cells and tissues and then assessed the effects of HOTAIR on modulation of gastric cancer cell sensitivity to cisplatin and the underlying molecular events. The data showed that HOTAIR was significantly upregulated in cisplatin-resistant gastric cancer cells and tissues compared with control cells and noncancerous gastric tissues. Overexpression of HOTAIR enhanced gastric cancer cell proliferation, promoted cell cycle G1/S transition, but decreased tumor cell apoptosis. Furthermore, HOTAIR was shown to directly bind to and inhibit miR-126 expression and then to promote VEGFA and PIK3R2 expression and activate the PI3K/AKT/MRP1 pathway. In conclusion, the data demonstrated that high HOTAIR expression acted as a competitive endogenous RNA to promote cisplatin resistance in gastric cancer. Further study will evaluate HOTAIR expression as a biomarker to predict treatment response of cisplatin and explore inhibition of HOTAIR expression as a novel strategy for anti-cisplatin resistance in human gastric cancer.
Literatur
1.
Zurück zum Zitat Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer Suppl. 2015;136(5):E359–86.CrossRef Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer Suppl. 2015;136(5):E359–86.CrossRef
2.
Zurück zum Zitat Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nature reviews. Cancer. 2013;13(10):714–26.PubMed Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nature reviews. Cancer. 2013;13(10):714–26.PubMed
3.
Zurück zum Zitat Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497(7447):108–12.CrossRefPubMed Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497(7447):108–12.CrossRefPubMed
4.
Zurück zum Zitat Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, et al. Global identification of human transcribed sequences with genome tiling arrays. Science (New York, NY). 2004;306(5705):2242–6.CrossRef Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, et al. Global identification of human transcribed sequences with genome tiling arrays. Science (New York, NY). 2004;306(5705):2242–6.CrossRef
5.
Zurück zum Zitat Finishing the euchromatic sequence of the human genome. Nature. 2004;431(7011):931–45. Finishing the euchromatic sequence of the human genome. Nature. 2004;431(7011):931–45.
6.
Zurück zum Zitat Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477(7364):295–300.CrossRefPubMedPubMedCentral Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477(7364):295–300.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Hayes EL, Lewis-Wambi JS. Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA. Breast Cancer Res. 2015;17:40.CrossRefPubMedPubMedCentral Hayes EL, Lewis-Wambi JS. Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA. Breast Cancer Res. 2015;17:40.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Sun QL, Zhao CP, Wang TY, Hao XB, Wang XY, Zhang X, et al. Expression profile analysis of long non-coding RNA associated with vincristine resistance in colon cancer cells by next-generation sequencing. Gene. 2015;572(1):79–86.CrossRefPubMed Sun QL, Zhao CP, Wang TY, Hao XB, Wang XY, Zhang X, et al. Expression profile analysis of long non-coding RNA associated with vincristine resistance in colon cancer cells by next-generation sequencing. Gene. 2015;572(1):79–86.CrossRefPubMed
9.
Zurück zum Zitat Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science (New York, NY). 2010;329(5992):689–93.CrossRef Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science (New York, NY). 2010;329(5992):689–93.CrossRef
10.
Zurück zum Zitat Xue X, Yang YA, Zhang A, Fong KW, Kim J, Song B, et al. LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene. 2015. Xue X, Yang YA, Zhang A, Fong KW, Kim J, Song B, et al. LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene. 2015.
11.
Zurück zum Zitat Li J, Yang S, Su N, Wang Y, Yu J, Qiu H, et al. Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/beta-catenin pathway in human ovarian cancer. Tumour Biol : J Int Soc Oncodev Biol Med. 2015. Li J, Yang S, Su N, Wang Y, Yu J, Qiu H, et al. Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/beta-catenin pathway in human ovarian cancer. Tumour Biol : J Int Soc Oncodev Biol Med. 2015.
12.
Zurück zum Zitat Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011;147(2):358–69.CrossRefPubMedPubMedCentral Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011;147(2):358–69.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Lu MH, Tang B, Zeng S, Hu CJ, Xie R, Wu YY, et al. Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene. 2015. Lu MH, Tang B, Zeng S, Hu CJ, Xie R, Wu YY, et al. Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene. 2015.
15.
Zurück zum Zitat Zhu X, Li H, Long L, Hui L, Chen H, Wang X, et al. miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A. Acta Biochim Biophys Sin. 2012;44(6):519–26.CrossRefPubMed Zhu X, Li H, Long L, Hui L, Chen H, Wang X, et al. miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A. Acta Biochim Biophys Sin. 2012;44(6):519–26.CrossRefPubMed
16.
Zurück zum Zitat Zhu N, Zhang D, Xie H, Zhou Z, Chen H, Hu T, et al. Endothelial-specific intron-derived miR-126 is down-regulated in human breast cancer and targets both VEGFA and PIK3R2. Mol Cell Biochem. 2011;351(1–2):157–64.CrossRefPubMed Zhu N, Zhang D, Xie H, Zhou Z, Chen H, Hu T, et al. Endothelial-specific intron-derived miR-126 is down-regulated in human breast cancer and targets both VEGFA and PIK3R2. Mol Cell Biochem. 2011;351(1–2):157–64.CrossRefPubMed
17.
Zurück zum Zitat Nath S, Daneshvar K, Roy LD, Grover P, Kidiyoor A, Mosley L, et al. MUC1 induces drug resistance in pancreatic cancer cells via upregulation of multidrug resistance genes. Oncogenesis. 2013;2:e51.CrossRefPubMedPubMedCentral Nath S, Daneshvar K, Roy LD, Grover P, Kidiyoor A, Mosley L, et al. MUC1 induces drug resistance in pancreatic cancer cells via upregulation of multidrug resistance genes. Oncogenesis. 2013;2:e51.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Xu HB, Shen FM, Lv QZ. Celecoxib enhanced the cytotoxic effect of cisplatin in chemo-resistant gastric cancer xenograft mouse models through a cyclooxygenase-2-dependent manner. Eur J Pharmacol. 2016;776:1–8.CrossRefPubMed Xu HB, Shen FM, Lv QZ. Celecoxib enhanced the cytotoxic effect of cisplatin in chemo-resistant gastric cancer xenograft mouse models through a cyclooxygenase-2-dependent manner. Eur J Pharmacol. 2016;776:1–8.CrossRefPubMed
19.
Zurück zum Zitat Kimura A, Ogata K, Altan B, Yokobori T, Ide M, Mochiki E, et al. Nuclear heat shock protein 110 expression is associated with poor prognosis and chemotherapy resistance in gastric cancer. Oncotarget. 2016. Kimura A, Ogata K, Altan B, Yokobori T, Ide M, Mochiki E, et al. Nuclear heat shock protein 110 expression is associated with poor prognosis and chemotherapy resistance in gastric cancer. Oncotarget. 2016.
20.
Zurück zum Zitat Sun Y, Zheng S, Torossian A, Speirs CK, Schleicher S, Giacalone NJ, et al. Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells. Int J Radiat Oncol Biol Phys. 2012;82(3):e563–72.CrossRefPubMed Sun Y, Zheng S, Torossian A, Speirs CK, Schleicher S, Giacalone NJ, et al. Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells. Int J Radiat Oncol Biol Phys. 2012;82(3):e563–72.CrossRefPubMed
21.
Zurück zum Zitat Noel EE, Yeste-Velasco M, Mao X, Perry J, Kudahetti SC, Li NF, et al. The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers. Am J Pathol. 2010;176(6):2607–15.CrossRefPubMedPubMedCentral Noel EE, Yeste-Velasco M, Mao X, Perry J, Kudahetti SC, Li NF, et al. The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers. Am J Pathol. 2010;176(6):2607–15.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Li T, Mo X, Fu L, Xiao B, Guo J. Molecular mechanisms of long noncoding RNAs on gastric cancer. Oncotarget. 2016. Li T, Mo X, Fu L, Xiao B, Guo J. Molecular mechanisms of long noncoding RNAs on gastric cancer. Oncotarget. 2016.
23.
Zurück zum Zitat Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, et al. The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One. 2013;8(10):e77293.CrossRefPubMedPubMedCentral Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, et al. The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One. 2013;8(10):e77293.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Li J, Yang S, Su N, Wang Y, Yu J, Qiu H, et al. Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/beta-catenin pathway in human ovarian cancer. Tumour Biol. 2016;37(2):2057–65.CrossRefPubMed Li J, Yang S, Su N, Wang Y, Yu J, Qiu H, et al. Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/beta-catenin pathway in human ovarian cancer. Tumour Biol. 2016;37(2):2057–65.CrossRefPubMed
25.
Zurück zum Zitat Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.CrossRefPubMedPubMedCentral Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Yoon JH, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, et al. Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun. 2013;4:2939.CrossRefPubMedPubMedCentral Yoon JH, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, et al. Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun. 2013;4:2939.CrossRefPubMedPubMedCentral
27.
28.
Zurück zum Zitat Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.CrossRefPubMedPubMedCentral Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Yu Q, Liu SL, Wang H, Shi G, Yang P, Chen XL. miR-126 suppresses the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin. Asian Pac J Cancer Prev. 2014;14(11):6569–72.CrossRefPubMed Yu Q, Liu SL, Wang H, Shi G, Yang P, Chen XL. miR-126 suppresses the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin. Asian Pac J Cancer Prev. 2014;14(11):6569–72.CrossRefPubMed
30.
Zurück zum Zitat Jiang L, Tao C, He A, He X. Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate. World J Surg Oncol. 2014;12:383.CrossRefPubMedPubMedCentral Jiang L, Tao C, He A, He X. Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate. World J Surg Oncol. 2014;12:383.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Jiang L, He A, Zhang Q, Tao C. miR-126 inhibits cell growth, invasion, and migration of osteosarcoma cells by downregulating ADAM-9. Tumour Biol. 2014;35(12):12645–54.CrossRefPubMed Jiang L, He A, Zhang Q, Tao C. miR-126 inhibits cell growth, invasion, and migration of osteosarcoma cells by downregulating ADAM-9. Tumour Biol. 2014;35(12):12645–54.CrossRefPubMed
32.
Zurück zum Zitat Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science (New York, NY). 1992;258(5088):1650–4.CrossRef Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science (New York, NY). 1992;258(5088):1650–4.CrossRef
33.
Zurück zum Zitat Chang XB. A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1. Cancer Metastasis Rev. 2007;26(1):15–37.CrossRefPubMed Chang XB. A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1. Cancer Metastasis Rev. 2007;26(1):15–37.CrossRefPubMed
34.
Zurück zum Zitat Liu LY, Wang W, Zhao LY, Guo B, Yang J, Zhao XG, et al. Mir-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2. Int J Oncol. 2014;45(3):1257–65.PubMed Liu LY, Wang W, Zhao LY, Guo B, Yang J, Zhao XG, et al. Mir-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2. Int J Oncol. 2014;45(3):1257–65.PubMed
Metadaten
Titel
LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes
verfasst von
Jin Yan
Yini Dang
Shiyu Liu
Yifeng Zhang
Guoxin Zhang
Publikationsdatum
30.11.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 12/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5448-5

Weitere Artikel der Ausgabe 12/2016

Tumor Biology 12/2016 Zur Ausgabe

Nodal-negativ nach neoadjuvanter Chemo: Axilladissektion verzichtbar?

03.05.2024 Mammakarzinom Nachrichten

Wenn bei Mammakarzinomen durch eine neoadjuvante Chemotherapie ein Downstaging von nodal-positiv zu nodal-negativ gelingt, scheint es auch ohne Axilladissektion nur selten zu axillären Rezidiven zu kommen.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

02.05.2024 Prostatakarzinom Nachrichten

Eine adjuvante Radiotherapie nach radikaler Prostata-Op. bringt den Betroffenen wahrscheinlich keinen Vorteil. Im Gegenteil: Durch die Bestrahlung steigt offenbar das Risiko für Harn- und Stuhlinkontinenz.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärzte und Psychotherapeuten.

Update Onkologie

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