Skip to main content
Erschienen in: Tumor Biology 2/2016

29.08.2015 | Original Article

Upregulation of miR-129-5p affects laryngeal cancer cell proliferation, invasiveness, and migration by affecting STAT3 expression

verfasst von: Na Shen, Xinsheng Huang, Jun Li

Erschienen in: Tumor Biology | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

microRNA-129-5p may have a relationship with laryngeal squamous cell carcinoma (LSCC), but the expression and function of miRNA-129-5p are not fully understood. This study was performed to investigate the expression and function of miRNA-129-5p in LSCC and its effects on STAT3. HBE and Hep-2 cells were cultured and analyzed by western blotting and real-time PCR. miR-129-5p expression was detected by real-time PCR. Hep-2 cells were transfected with a miR-129-5p expression vector. Cell proliferation, invasion, migration, cell cycle, and apoptosis assays were used to determine the role of miRNA-129-5p in the growth, invasion, and migration of LSCC cells and to determine the importance of STAT3 in these effects. STAT3 mRNA expression in Hep-2 cells was significantly higher than that in HBE cells (P < 0.05). miR-129-5p expression detected by real-time PCR showed that it was expressed at a lower level in Hep-2 cells than in HBE cells (P < 0.05). Compared with the control cells, the transfected cells showed lower STAT3 mRNA expression. For up to 7 days in culture, the transfected cells showed lower proliferation than the control cells (P < 0.05). After 24 h in culture, the apoptosis rate in miR-129-5p-transfected cells was 3.48 ± 0.38 %, while the rate in control cells was 0.92 ± 0.09 % (P = 0.0028), but the statistical significance was lost after 72 h in culture (P = 0.3180). The invasion and migration of the cells were inhibited after 24 and 72 h in culture when the miR-129-5p expression in Hep-2 cells was upregulated (P = 0.0037 and 0.00383, respectively), while there was no statistically significant difference at 48 h (P = 0.0712). STAT3 expression could be suppressed by the upregulation of miR-129-5p expression. Both the proliferation and migration of tumor cells were suppressed when the level of STAT3 expression was decreased. The apoptosis rate of tumor cells was also increased. Based on these data, we suggest that miR-129-5p may directly inhibit STAT3 expression and play an important role in the development of LSCC.
Literatur
1.
Zurück zum Zitat Mirisola V, Mora R, Esposito AI, Guastini L, Tabacchiera F, Paleari L, et al. A prognostic multigene classifier for squamous cell carcinomas of the larynx. Cancer Lett. 2011;307:37–46.CrossRefPubMed Mirisola V, Mora R, Esposito AI, Guastini L, Tabacchiera F, Paleari L, et al. A prognostic multigene classifier for squamous cell carcinomas of the larynx. Cancer Lett. 2011;307:37–46.CrossRefPubMed
2.
Zurück zum Zitat Bartel DP. Micrornas: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMed Bartel DP. Micrornas: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMed
4.
5.
Zurück zum Zitat Liu M, Wu H, Liu T, Li Y, Wang F, Wan H, et al. Regulation of the cell cycle gene, btg2, by mir-21 in human laryngeal carcinoma. Cell Res. 2009;19:828–39.CrossRefPubMed Liu M, Wu H, Liu T, Li Y, Wang F, Wan H, et al. Regulation of the cell cycle gene, btg2, by mir-21 in human laryngeal carcinoma. Cell Res. 2009;19:828–39.CrossRefPubMed
6.
Zurück zum Zitat Cai KM, Bao XL, Kong XH, Jinag W, Mao MR, Chu JS, et al. Hsa-mir-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-met. Int J Mol Med. 2010;25:565–71.CrossRefPubMed Cai KM, Bao XL, Kong XH, Jinag W, Mao MR, Chu JS, et al. Hsa-mir-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-met. Int J Mol Med. 2010;25:565–71.CrossRefPubMed
7.
Zurück zum Zitat Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, et al. Gene therapy with dominant-negative stat3 suppresses growth of the murine melanoma b16 tumor in vivo. Cancer Res. 1999;59:5059–63.PubMed Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, et al. Gene therapy with dominant-negative stat3 suppresses growth of the murine melanoma b16 tumor in vivo. Cancer Res. 1999;59:5059–63.PubMed
8.
Zurück zum Zitat Liu B, Ren Z, Shi Y, Guan C, Pan Z, Zong Z. Activation of signal transducers and activators of transcription 3 and overexpression of its target gene cyclind1 in laryngeal carcinomas. Laryngoscope. 2008;118:1976–80.CrossRefPubMed Liu B, Ren Z, Shi Y, Guan C, Pan Z, Zong Z. Activation of signal transducers and activators of transcription 3 and overexpression of its target gene cyclind1 in laryngeal carcinomas. Laryngoscope. 2008;118:1976–80.CrossRefPubMed
9.
Zurück zum Zitat Zhao X, Zang W, Liang H, Ji W. Overexpression of mir −155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting socs1 and stat3. PLoS ONE. 2013;8:e56395.CrossRefPubMedPubMedCentral Zhao X, Zang W, Liang H, Ji W. Overexpression of mir −155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting socs1 and stat3. PLoS ONE. 2013;8:e56395.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Dreher A, Rossing M, Kaczkowski B, Andersen DK, Larsen TJ, Christophersen MK, et al. Differential expression of cellular micrornas in hpv 11, −16, and −45 transfected cells. Biochem Biophys Res Commun. 2011;412:20–5.CrossRefPubMed Dreher A, Rossing M, Kaczkowski B, Andersen DK, Larsen TJ, Christophersen MK, et al. Differential expression of cellular micrornas in hpv 11, −16, and −45 transfected cells. Biochem Biophys Res Commun. 2011;412:20–5.CrossRefPubMed
11.
Zurück zum Zitat Ogawa R, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Katada T, et al. Expression profiling of micro-rnas in human esophageal squamous cell carcinoma using rt-pcr. Med Mol Morphol. 2009;42:102–9.CrossRefPubMed Ogawa R, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Katada T, et al. Expression profiling of micro-rnas in human esophageal squamous cell carcinoma using rt-pcr. Med Mol Morphol. 2009;42:102–9.CrossRefPubMed
12.
Zurück zum Zitat Shen R, Pan S, Qi S, Lin X, Cheng S. Epigenetic repression of microrna-129-2 leads to overexpression of sox4 in gastric cancer. Biochem Biophys Res Commun. 2010;394:1047–52.CrossRefPubMed Shen R, Pan S, Qi S, Lin X, Cheng S. Epigenetic repression of microrna-129-2 leads to overexpression of sox4 in gastric cancer. Biochem Biophys Res Commun. 2010;394:1047–52.CrossRefPubMed
13.
Zurück zum Zitat Birks DK, Barton V, Donson AM, Handler MH, Vibhakar R, Foreman NK. Survey of microrna expression in pediatric brain tumors. Pediatr Blood Cancer. 2011;56:211–6.CrossRefPubMed Birks DK, Barton V, Donson AM, Handler MH, Vibhakar R, Foreman NK. Survey of microrna expression in pediatric brain tumors. Pediatr Blood Cancer. 2011;56:211–6.CrossRefPubMed
14.
Zurück zum Zitat Liu Y, Hei Y, Shu Q, Dong J, Gao Y, Fu H, et al. Vcp/p97, down-regulated by microrna-129-5p, could regulate the progression of hepatocellular carcinoma. PLoS One. 2012;7:e35800.CrossRefPubMedPubMedCentral Liu Y, Hei Y, Shu Q, Dong J, Gao Y, Fu H, et al. Vcp/p97, down-regulated by microrna-129-5p, could regulate the progression of hepatocellular carcinoma. PLoS One. 2012;7:e35800.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Li M, Tian L, Wang L, Yao H, Zhang J, Lu J, et al. Down-regulation of mir-129-5p inhibits growth and induces apoptosis in laryngeal squamous cell carcinoma by targeting apc. PLoS One. 2013;8:e77829.CrossRefPubMedPubMedCentral Li M, Tian L, Wang L, Yao H, Zhang J, Lu J, et al. Down-regulation of mir-129-5p inhibits growth and induces apoptosis in laryngeal squamous cell carcinoma by targeting apc. PLoS One. 2013;8:e77829.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Wang J, Li X, Chen Y, Lu X. Expression of stat3 and p-stat3 in laryngeal carcinoma and its clinical significance. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2007;21:113–5.PubMed Wang J, Li X, Chen Y, Lu X. Expression of stat3 and p-stat3 in laryngeal carcinoma and its clinical significance. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2007;21:113–5.PubMed
17.
Zurück zum Zitat Aaronson DS, Horvath C. A road map for those who don't know jak-stat. Science. 2002;296:1653–5.CrossRefPubMed Aaronson DS, Horvath C. A road map for those who don't know jak-stat. Science. 2002;296:1653–5.CrossRefPubMed
18.
Zurück zum Zitat Li HD, Huang C, Huang KJ, Wu WD, Jiang T, Cao J, et al. Stat3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice. PLoS One. 2011;6:e25941.CrossRefPubMedPubMedCentral Li HD, Huang C, Huang KJ, Wu WD, Jiang T, Cao J, et al. Stat3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice. PLoS One. 2011;6:e25941.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Huang C, Cao J, Huang KJ, Zhang F, Jiang T, Zhu L, et al. Inhibition of stat3 activity with ag490 decreases the invasion of human pancreatic cancer cells in vitro. Cancer Sci. 2006;97:1417–23.CrossRefPubMed Huang C, Cao J, Huang KJ, Zhang F, Jiang T, Zhu L, et al. Inhibition of stat3 activity with ag490 decreases the invasion of human pancreatic cancer cells in vitro. Cancer Sci. 2006;97:1417–23.CrossRefPubMed
20.
Zurück zum Zitat Masuda M, Suzui M, Yasumatu R, Nakashima T, Kuratomi Y, Azuma K, et al. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin d1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res. 2002;62:3351–5.PubMed Masuda M, Suzui M, Yasumatu R, Nakashima T, Kuratomi Y, Azuma K, et al. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin d1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res. 2002;62:3351–5.PubMed
21.
Zurück zum Zitat Choi JH, Ahn M, Park CK, Han HX, Kwon SJ, Lee YY, et al. Phospho-stat3 expression and correlation with vegf, p53, and bcl-2 in gastric carcinoma using tissue microarray. APMIS. 2006;114:619–25.CrossRefPubMed Choi JH, Ahn M, Park CK, Han HX, Kwon SJ, Lee YY, et al. Phospho-stat3 expression and correlation with vegf, p53, and bcl-2 in gastric carcinoma using tissue microarray. APMIS. 2006;114:619–25.CrossRefPubMed
22.
Zurück zum Zitat Greten FR, Weber C, Greten TF, Schneider G, Wagner M, Adler G, et al. Stat3 and nf-kappab activation prevents apoptosis in pancreatic carcinogenesis. Gastroenterology. 2002;123:2052–63.CrossRefPubMed Greten FR, Weber C, Greten TF, Schneider G, Wagner M, Adler G, et al. Stat3 and nf-kappab activation prevents apoptosis in pancreatic carcinogenesis. Gastroenterology. 2002;123:2052–63.CrossRefPubMed
Metadaten
Titel
Upregulation of miR-129-5p affects laryngeal cancer cell proliferation, invasiveness, and migration by affecting STAT3 expression
verfasst von
Na Shen
Xinsheng Huang
Jun Li
Publikationsdatum
29.08.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3969-y

Weitere Artikel der Ausgabe 2/2016

Tumor Biology 2/2016 Zur Ausgabe

Update Onkologie

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