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Journal of Gastrointestinal Cancer
Erschienen in: Journal of Gastrointestinal Cancer 2/2017

14.09.2016 | Original Research

siRNA-Mediated Silencing of HMGA2 Induces Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma

verfasst von: Sahar Esmailzadeh, Behzad Mansoori, Ali Mohammadi, Dariush Shanehbandi, Behzad Baradaran

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 2/2017

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Abstract

Purpose

Overexpression of HMGA2, known as small non-histone chromosomal protein, is associated with progression of various tumors, including colorectal cancers. The aim of this study was to investigate the effect of a specific HMGA2 siRNA on apoptosis and cell cycle of HCT-116 (colorectal carcinoma) cells.

Methods

The cells were transfected with siRNAs using a transfection reagent. The cytotoxic effects of HMGA2 siRNA on colorectal carcinoma cells were determined using MTT assay. Relative HMGA2 mRNA and protein levels were measured by QRT-PCR and western blotting, respectively. Apoptosis was measured by a TUNEL test based on labeling of DNA strand breaks. We also evaluated caspase-3, caspase-8, and caspase-9 expression by QRTPCR to determine which pathway is involved in apoptosis. Cell cycle was assessed by FACS and cell cycle analysis using PI DNA staining.

Results

HMGA2 siRNA significantly reduced both mRNA and protein expression levels 48 h after transfection and dose-dependent manner in colorectal carcinoma cells. We also showed that the silencing of HMGA2 led to the induction of apoptosis through intrinsic pathway and cell cycle arrest in G2/M phases of interphase in HCT-116 cells in vitro.

Conclusions

These results propose that HMGA2 might play an important role in the progression of colorectal carcinoma and might be a potential therapeutic target for trigger apoptosis and cell cycle arrest in colorectal carcinoma.
Literatur
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
2.
Lotfipour F, Hallaj-Nezhadi S, Valizadeh H, Dastmalchi S, Baradaran B, Jalali MB, Dobakhti F. Preparation of chitosan-plasmid DNA nanoparticles encoding interleukin-12 and their expression in CT-26 colon carcinoma cells. Journal of Pharmacy & Pharmaceutical Sciences. 2011;14(2):181–95.CrossRef
3.
Mohammadi A, Mansoori B, Aghapour M, Baradaran PC, Shajari N, Davudian S, Salehi S, Baradaran B. The herbal medicine Utrica dioica inhibits proliferation of colorectal cancer cell line by inducing apoptosis and arrest at the G2/M phase. Journal of Gastrointestinal Cancer. 2016:1–9.
4.
Valiyari S, Jahanban-Esfahlan R, Shahneh FZ, Yaripour S, Baradaran B, Delazar A. Cytotoxic and apoptotic activity of Scrophularia oxysepala in MCF-7 human breast cancer cells. Toxicol Environ Chem. 2013;95(7):1208–20.CrossRef
5.
Luwor R, Baradaran B, Taylor L, Iaria J, Nheu T, Amiry N, Hovens C, Wang B, Kaye A, Zhu H. Targeting Stat3 and Smad7 to restore TGF-β cytostatic regulation of tumor cells in vitro and in vivo. Oncogene. 2013;32(19):2433–41.CrossRefPubMed
6.
7.
Natarajan S, Hombach-Klonisch S, Dröge P, Klonisch T. HMGA2 inhibits apoptosis through interaction with ATR-CHK1 signaling complex in human cancer cells. Neoplasia. 2013;15(3):263–IN213.CrossRefPubMedPubMedCentral
8.
Cleynen I, Van de Ven WJ. The HMGA proteins: a myriad of functions (Review). Int J Oncol. 2008;32(2):289–305.PubMed
9.
Tessari MA, Gostissa M, Altamura S, Sgarra R, Rustighi A, Salvagno C, Caretti G, Imbriano C, Mantovani R, Del Sal G. Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2. Mol Cell Biol. 2003;23(24):9104–16.CrossRefPubMedPubMedCentral
10.
De Martino I, Visone R, Wierinckx A, Palmieri D, Ferraro A, Cappabianca P, Chiappetta G, Forzati F, Lombardi G, Colao A. HMGA proteins up-regulate CCNB2 gene in mouse and human pituitary adenomas. Cancer Res. 2009;69(5):1844–50.CrossRefPubMed
11.
Manfioletti G, Giancotti V, Bandiera A, Buratti E, Sautièere P, Cary P, Crane-Robinson C, Coles B, Goodwin G. cDNA cloning of the HML-C phosphoprotein, a nclear protein associated with neoplastic and undifferentiated phenotypes. Nucleic Acids Res. 1991;19(24):6793–7.CrossRefPubMedPubMedCentral
12.
Zhou X, Benson KF, Ashar HR, Chada K (1995) Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C.
13.
Rogalla P, Drechsler K, Frey G, Hennig Y, Helmke B, Bonk U, Bullerdiek J. HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors. Am J Pathol. 1996;149(3):775.PubMedPubMedCentral
14.
Guang-meng X, Hai-na Z, Xiao-feng T, Mei S, Xue-dong F. Effect of HMGA2 shRNA on the cell proliferation and invasion of human colorectal cancer SW480 cells in vitro. CHEMICAL RESEARCH IN CHINESE UNIVERSITES. 2012;28(2):264–8.
15.
Belge G, Meyer A, Klemke M, Burchardt K, Stern C, Wosniok W, Loeschke S, Bullerdiek J. Upregulation of HMGA2 in thyroid carcinomas: a novel molecular marker to distinguish between benign and malignant follicular neoplasias. Genes Chromosom Cancer. 2008;47(1):56–63.CrossRefPubMed
16.
Rogalla P, Drechsler K, Kazmierczak B, Rippe V, Bonk U, Bullerdiek J. Expression of HMGI-C, a member of the high mobility group protein family, in a subset of breast cancers: relationship to histologic grade. Mol Carcinog. 1997;19(3):153–6.CrossRefPubMed
17.
Langelotz C, Schmid P, Jakob C, Heider U, Wernecke K, Possinger K, Sezer O. Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer. Br J Cancer. 2003;88(9):1406–10.CrossRefPubMedPubMedCentral
18.
Di Cello F, Hillion J, Hristov A, Wood LJ, Mukherjee M, Schuldenfrei A, Kowalski J, Bhattacharya R, Ashfaq R, Resar LM. HMGA2 participates in transformation in human lung cancer. Mol Cancer Res. 2008;6(5):743–50.CrossRefPubMedPubMedCentral
19.
Abe N, Watanabe T, Suzuki Y, Matsumoto N, Masaki T, Mori T, Sugiyama M, Chiappetta G, Fusco A, Atomi Y. An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue. Br J Cancer. 2003;89(11):2104–9.CrossRefPubMedPubMedCentral
20.
Hristov AC, Cope L, Reyes MD, Singh M, Iacobuzio-Donahue C, Maitra A, Resar L. HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. Mod Pathol. 2009;22(1):43–9.CrossRefPubMed
21.
Miyazawa J, Mitoro A, Kawashiri S, Chada KK, Imai K. Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity. Cancer Res. 2004;64(6):2024–9.CrossRefPubMed
22.
Malek A, Bakhidze E, Noske A, Sers C, Aigner A, Schäfer R, Tchernitsa O. HMGA2 gene is a promising target for ovarian cancer silencing therapy. Int J Cancer. 2008;123(2):348–56.CrossRefPubMed
23.
Park S-M, Shell S, Radjabi AR, Schickel R, Feig C, Boyerinas B, Dinulescu DM, Lengyel E, Peter ME. Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2. Cell Cycle. 2007;6(21):2585–90.CrossRefPubMed
24.
Yang G, Zhang L, Bo J, Hou K, Cai X, Chen Y, Li H, Liu D, Huang Y. Overexpression of HMGA2 in bladder cancer and its association with clinicopathologic features and prognosis: HMGA2 as a prognostic marker of bladder cancer. European Journal of Surgical Oncology (EJSO). 2011;37(3):265–71.CrossRef
25.
Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K, Mori M. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res. 2008;14(8):2334–40.CrossRefPubMed
26.
Huang M-L, Chen C-C, Chang L-C. Gene expressions of HMGI-C and HMGI (Y) are associated with stage and metastasis in colorectal cancer. Int J Color Dis. 2009;24(11):1281–6.CrossRef
27.
Wang X, Liu X, Li AY-J, Chen L, Lai L, Lin HH, Hu S, Yao L, Peng J, Loera S. Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers. Clin Cancer Res. 2011;17(8):2570–80.CrossRefPubMedPubMedCentral
28.
Mansoori B, Mohammadi A, Goldar S, Shanehbandi D, Mohammadnejad L, Baghbani E, Kazemi T, Kachalaki S, Baradaran B (2016) Silencing of high mobility group isoform IC (HMGI-C) enhances paclitaxel chemosensitivity in breast adenocarcinoma cells (MDA-MB-468).
29.
Karami H, Baradaran B, Esfahani A, Estiar MA, Naghavi-Behzad M, Sakhinia M, Sakhinia E. siRNA-Mediated silencing of survivin inhibits proliferation and enhances etoposidechemosensitivity in acute myeloid leukemia cells. Asian Pac J Cancer Prev. 2013;14(12):7719–24.CrossRefPubMed
30.
Zheng TS, Hunot S, Kuida K, Momoi T, Srinivasan A, Nicholson DW, Lazebnik Y, Flavell RA. Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation. Nat Med. 2000;6(11):1241–7.CrossRefPubMed
31.
Mansoori B, Mohammadi A, Shirjang S, Baradaran B (2016) HMGI-C suppressing induces P53/caspase9 axis to regulate apoptosis in breast adenocarcinoma cells. Cell Cycle (just-accepted):00–00
32.
Cuddihy AR, O’Connell MJ. Cell-cycle responses to DNA damage in G2. Int Rev Cytol. 2003;222:99–140.CrossRefPubMed
33.
Chiappetta G, Ferraro A, Vuttariello E, Monaco M, Galdiero F, De Simone V, Califano D, Pallante P, Botti G, Pezzullo L. HMGA2 mRNA expression correlates with the malignant phenotype in human thyroid neoplasias. Eur J Cancer. 2008;44(7):1015–21.CrossRefPubMed
34.
Gattas GJ, Quade BJ, Nowak RA, Morton CC. HMGIC expression in human adult and fetal tissues and in uterine leiomyomata. Genes Chromosom Cancer. 1999;25(4):316–22.CrossRefPubMed
35.
Hebert C, Norris K, Scheper MA, Nikitakis N, Sauk JJ. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer. 2007;6(1).
36.
Mahajan A, Liu Z, Gellert L, Zou X, Yang G, Lee P, Yang X, Wei J-J. HMGA2: a biomarker significantly overexpressed in high-grade ovarian serous carcinoma. Mod Pathol. 2010;23(5):673–81.CrossRefPubMed
37.
Meyer B, Loeschke S, Schultze A, Weigel T, Sandkamp M, Goldmann T, Vollmer E, Bullerdiek J. HMGA2 overexpression in non-small cell lung cancer. Mol Carcinog. 2007;46(7):503–11.CrossRefPubMed
38.
Wu J, Liu Z, Shao C, Gong Y, Hernando E, Lee P, Narita M, Muller W, Liu J, Wei J-J. HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes. Cancer Res. 2011;71(2):349–59.CrossRefPubMedPubMedCentral
39.
Montazami N, Kheirandish M, Majidi J, Yousefi M, Yousefi B, Mohamadnejad L, Shanebandi D, Estiar M, Khaze V, Mansoori B. siRNA-mediated silencing of MDR1 reverses the resistance to oxaliplatin in SW480/OxR colon cancer cells. Cellular and molecular biology (Noisy-le-Grand, France). 2015;61(2):98.
40.
41.
Yang M, Mattes J. Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs. Pharmacol Ther. 2008;117(1):94–104.CrossRefPubMed
42.
Shan G. RNA interference as a gene knockdown technique. Int J Biochem Cell Biol. 2010;42(8):1243–51.CrossRefPubMed
43.
Kachalaki S, Baradaran B, Majidi J, Yousefi M, Shanehbandi D, Mohammadinejad S, Mansoori B. Reversal of chemoresistance with small interference RNA (siRNA) in etoposide resistant acute myeloid leukemia cells (HL-60). Biomedicine & Pharmacotherapy. 2015;75:100–4.CrossRef
44.
Mansoori B, Shotorbani SS, Baradaran B. RNA interference and its role in cancer therapy. Advanced pharmaceutical bulletin. 2014;4(4).
45.
Mansoori B, Mohammadi A, Shir Jang S, Baradaran B. Mechanisms of immune system activation in mammalians by small interfering RNA (siRNA. Artificial cells, nanomedicine, and biotechnology. 2015:1–8.
46.
Musavi Shenas SMH, Mansoori B, Mohammadi A, Salehi S, Kaffash B, Talebi B, Babaloo Z, Shanehbandi D, Baradaran B. SiRNA-mediated silencing of snail-1 induces apoptosis and alters micro RNA expression in human urinary bladder cancer cell line. Artif Cells Nanomed Biotechnol. 2016:1–6.
47.
Brantl S. Antisense-RNA regulation and RNA interference. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression. 2002;1575(1):15–25.CrossRef
48.
Aoki Y, Cioca D, Oidaira H, Kamiya J, Kiyosawa K. RNA interference may be more potent than antisense RNA in human cancer cell lines. Clin Exp Pharmacol Physiol. 2003;30(1–2):96–102.CrossRefPubMed
Metadaten
Titel
siRNA-Mediated Silencing of HMGA2 Induces Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma
verfasst von
Sahar Esmailzadeh
Behzad Mansoori
Ali Mohammadi
Dariush Shanehbandi
Behzad Baradaran
Publikationsdatum
14.09.2016
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 2/2017
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-016-9871-z

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