Skip to main content
Erschienen in: Medical Oncology 2/2013

01.06.2013 | Original Paper

miR-22 is down-regulated in gastric cancer, and its overexpression inhibits cell migration and invasion via targeting transcription factor Sp1

verfasst von: Mei-Mei Guo, Li-Hua Hu, Yong-Qiang Wang, Peng Chen, Jian-Guo Huang, Ning Lu, Jiang-Hong He, Cheng-Gong Liao

Erschienen in: Medical Oncology | Ausgabe 2/2013

Einloggen, um Zugang zu erhalten

Abstract

Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Recently, miR-22 has been identified as a tumor-suppressing microRNA in many human cancers. However, the specific function of miR-22 in gastric cancer is unclear at this point. In this study, we first measured miR-22 expression level in 30 pairs of gastric cancer and matched normal tissues, two normal and six gastric cancer cell lines by real-time quantitative RT-PCR. We found that the expression of miR-22 in gastric cancer tissues and cell lines was much lower than that in normal control, respectively. Transfection of miR-22 expression plasmid could significantly inhibit the cell migration and invasion in SGC-7901 and NCL-N87 gastric cancer cell lines. Moreover, we also showed that Sp1 was negatively regulated by miR-22 at the posttranscriptional level, via a specific target site within the 3′UTR by luciferase reporter assay. The expression of Sp1 was inversely correlated with miR-22 expression in gastric cancer tissues, and knockdown of Sp1 by siRNA inhibited cell malignant behaviors. Thus, our findings suggest that miR-22 acts as tumor suppressor by targeting the Sp1 gene and inhibiting gastric cancer cell migration and invasion. The findings of this study contribute to current understanding of the functions of miR-22 in gastric cancer.
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef
2.
Zurück zum Zitat Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.PubMed Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.PubMed
3.
Zurück zum Zitat Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.PubMed Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.PubMed
5.
Zurück zum Zitat Crone SG, Jacobsen A, Federspiel B, Bardram L, Krogh A, Lund AH, et al. microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-kappaB by targeting CARD10 and COPS8 in gastric cancer. Mol Cancer. 2012;11:71.PubMedCrossRef Crone SG, Jacobsen A, Federspiel B, Bardram L, Krogh A, Lund AH, et al. microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-kappaB by targeting CARD10 and COPS8 in gastric cancer. Mol Cancer. 2012;11:71.PubMedCrossRef
6.
7.
Zurück zum Zitat Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115:787–98.PubMedCrossRef Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115:787–98.PubMedCrossRef
8.
Zurück zum Zitat Xiong J, Du Q, Liang Z. Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein. Oncogene. 2010;29:4980–8.PubMedCrossRef Xiong J, Du Q, Liang Z. Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein. Oncogene. 2010;29:4980–8.PubMedCrossRef
9.
Zurück zum Zitat Bar N, Dikstein R. miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. PLoS ONE. 2010;5:e10859.PubMedCrossRef Bar N, Dikstein R. miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. PLoS ONE. 2010;5:e10859.PubMedCrossRef
10.
Zurück zum Zitat Ting Y, Medina DJ, Strair RK, Schaar DG. Differentiation-associated miR-22 represses Max expression and inhibits cell cycle progression. Biochem Biophys Res Commun. 2010;394:606–11.PubMedCrossRef Ting Y, Medina DJ, Strair RK, Schaar DG. Differentiation-associated miR-22 represses Max expression and inhibits cell cycle progression. Biochem Biophys Res Commun. 2010;394:606–11.PubMedCrossRef
11.
Zurück zum Zitat Tsuchiya N, Izumiya M, Ogata-Kawata H, Okamoto K, Fujiwara Y, Nakai M, et al. Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res. 2011;71:4628–39.PubMedCrossRef Tsuchiya N, Izumiya M, Ogata-Kawata H, Okamoto K, Fujiwara Y, Nakai M, et al. Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res. 2011;71:4628–39.PubMedCrossRef
12.
Zurück zum Zitat Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–8.PubMedCrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–8.PubMedCrossRef
13.
Zurück zum Zitat Liao CG, Kong LM, Song F, Xing JL, Wang LX, Sun ZJ, et al. Characterization of basigin isoforms and the inhibitory function of basigin-3 in human hepatocellular carcinoma proliferation and invasion. Mol Cell Biol. 2011;31:2591–604.PubMedCrossRef Liao CG, Kong LM, Song F, Xing JL, Wang LX, Sun ZJ, et al. Characterization of basigin isoforms and the inhibitory function of basigin-3 in human hepatocellular carcinoma proliferation and invasion. Mol Cell Biol. 2011;31:2591–604.PubMedCrossRef
14.
Zurück zum Zitat Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H, et al. MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 2010;285:7986–94.PubMedCrossRef Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H, et al. MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 2010;285:7986–94.PubMedCrossRef
15.
Zurück zum Zitat Patel JB, Appaiah HN, Burnett RM, Bhat-Nakshatri P, Wang G, Mehta R, et al. Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. Oncogene. 2011;30:1290–301.PubMedCrossRef Patel JB, Appaiah HN, Burnett RM, Bhat-Nakshatri P, Wang G, Mehta R, et al. Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. Oncogene. 2011;30:1290–301.PubMedCrossRef
16.
Zurück zum Zitat Xu D, Takeshita F, Hino Y, Fukunaga S, Kudo Y, Tamaki A, et al. miR-22 represses cancer progression by inducing cellular senescence. J Cell Biol. 2011;193:409–24.PubMedCrossRef Xu D, Takeshita F, Hino Y, Fukunaga S, Kudo Y, Tamaki A, et al. miR-22 represses cancer progression by inducing cellular senescence. J Cell Biol. 2011;193:409–24.PubMedCrossRef
17.
Zurück zum Zitat Hasegawa K, Wakino S, Tanaka T, Kimoto M, Tatematsu S, Kanda T, et al. Dimethylarginine dimethylaminohydrolase 2 increases vascular endothelial growth factor expression through Sp1 transcription factor in endothelial cells. Arterioscler Thromb Vasc Biol. 2006;26:1488–94.PubMedCrossRef Hasegawa K, Wakino S, Tanaka T, Kimoto M, Tatematsu S, Kanda T, et al. Dimethylarginine dimethylaminohydrolase 2 increases vascular endothelial growth factor expression through Sp1 transcription factor in endothelial cells. Arterioscler Thromb Vasc Biol. 2006;26:1488–94.PubMedCrossRef
18.
Zurück zum Zitat Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, et al. Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma. J Cell Mol Med. 2011;15:1415–28.PubMedCrossRef Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, et al. Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma. J Cell Mol Med. 2011;15:1415–28.PubMedCrossRef
19.
Zurück zum Zitat Kong LM, Liao CG, Fei F, Guo X, Xing JL, Chen ZN. Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. Cancer Sci. 2010;101:1463–70.PubMedCrossRef Kong LM, Liao CG, Fei F, Guo X, Xing JL, Chen ZN. Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. Cancer Sci. 2010;101:1463–70.PubMedCrossRef
20.
Zurück zum Zitat Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, et al. microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. Br J Cancer. 2010;103:1215–20.PubMedCrossRef Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, et al. microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. Br J Cancer. 2010;103:1215–20.PubMedCrossRef
21.
Zurück zum Zitat He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.PubMedCrossRef He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.PubMedCrossRef
22.
Zurück zum Zitat Wang F, Li Y, Zhou J, Xu J, Peng C, Ye F, et al. miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol. 2011;179:2580–8.PubMedCrossRef Wang F, Li Y, Zhou J, Xu J, Peng C, Ye F, et al. miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol. 2011;179:2580–8.PubMedCrossRef
23.
Zurück zum Zitat Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. 1999;49(33–64):1. Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. 1999;49(33–64):1.
24.
Zurück zum Zitat Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell. 2004;116:499–509.PubMedCrossRef Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell. 2004;116:499–509.PubMedCrossRef
25.
Zurück zum Zitat Yao JC, Wang L, Wei D, Gong W, Hassan M, Wu TT, et al. Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer. Clin Cancer Res. 2004;10:4109–17.PubMedCrossRef Yao JC, Wang L, Wei D, Gong W, Hassan M, Wu TT, et al. Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer. Clin Cancer Res. 2004;10:4109–17.PubMedCrossRef
26.
Zurück zum Zitat Yuan P, Wang L, Wei D, Zhang J, Jia Z, Li Q, et al. Therapeutic inhibition of Sp1 expression in growing tumors by mithramycin a correlates directly with potent antiangiogenic effects on human pancreatic cancer. Cancer. 2007;110:2682–90.PubMedCrossRef Yuan P, Wang L, Wei D, Zhang J, Jia Z, Li Q, et al. Therapeutic inhibition of Sp1 expression in growing tumors by mithramycin a correlates directly with potent antiangiogenic effects on human pancreatic cancer. Cancer. 2007;110:2682–90.PubMedCrossRef
27.
Zurück zum Zitat Oue N, Aung PP, Mitani Y, Kuniyasu H, Nakayama H, Yasui W. Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression. Oncology. 2005;69(Suppl 1):17–22.PubMedCrossRef Oue N, Aung PP, Mitani Y, Kuniyasu H, Nakayama H, Yasui W. Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression. Oncology. 2005;69(Suppl 1):17–22.PubMedCrossRef
28.
30.
Zurück zum Zitat Sreekumar R, Sayan BS, Mirnezami AH, Sayan AE. MicroRNA Control of Invasion and Metastasis Pathways. Front Genet. 2011;2:58.PubMedCrossRef Sreekumar R, Sayan BS, Mirnezami AH, Sayan AE. MicroRNA Control of Invasion and Metastasis Pathways. Front Genet. 2011;2:58.PubMedCrossRef
Metadaten
Titel
miR-22 is down-regulated in gastric cancer, and its overexpression inhibits cell migration and invasion via targeting transcription factor Sp1
verfasst von
Mei-Mei Guo
Li-Hua Hu
Yong-Qiang Wang
Peng Chen
Jian-Guo Huang
Ning Lu
Jiang-Hong He
Cheng-Gong Liao
Publikationsdatum
01.06.2013
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2013
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0542-7

Weitere Artikel der Ausgabe 2/2013

Medical Oncology 2/2013 Zur Ausgabe

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Alter verschlechtert Prognose bei Endometriumkarzinom

11.05.2024 Endometriumkarzinom Nachrichten

Ein höheres Alter bei der Diagnose eines Endometriumkarzinoms ist mit aggressiveren Tumorcharakteristika assoziiert, scheint aber auch unabhängig von bekannten Risikofaktoren die Prognose der Erkrankung zu verschlimmern.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Update Onkologie

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