Abstract
Gastric cancer (GC) is the fourth most prevalent type of cancer worldwide, which is usually caused by the interaction between environmental and genetic factors, or epigenetic aspects. Referring to the non-coding RNAs, miR-128b has been reported to be associated with many tumour cases, and exerts distinct functions in different types of cancers. However, the function of miR-128b in GC onset and progression largely remains unknown. In the present study, we found that miR-128b expression was down-regulated in tissues from 18 GC patients and 3 carcinoma cell lines. In turn, over-expression of miR-128b suppressed GC cell proliferation, invasion and promoted apoptosis. Moreover, miR-128b was predicted to bind the 3′UTR of PDK1 gene using bioinformatic target-screening tools. Accordingly, ectopic expression of miR-128b inhibited the PDK1 expression at both transcriptional and post-transcriptional levels, and furthermore, the expression of gene tailed by the 3′UTR of PDK1 gene was significantly decreased in a dual-luciferase reporter assay, suggesting that PDK1 was a direct target of miR-128b in GC cells. In the conditon of miR-128b over-expression, we also observed spontaneous inactivation of the Akt/NF-κB signalling, implying PDK1 was a potential regulator of this pathway. In conclusion, our study shed some novel light on miR-128b-PDK1/Akt/NF-κB axis on GC progression.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Almhanna K, Strosberg J and Malafa M 2011 Targeting akt protein kinase in gastric cancer. Anticancer Res. 31 4387–4392
Bayascas JR 2008 Dissecting the role of the 3-phosphoinositide-dependent protein kinase-1 (pdk1) signalling pathways. Cell Cycle (Georgetown, Tex) 7 2978–2982
Belkhiri A, Dar AA, Zaika A, et al. 2008 T-darpp promotes cancer cell survival by up-regulation of bcl2 through akt-dependent mechanism. Cancer Res. 68 395–403
Dieterle AM, Bohler P, Keppeler H, et al. 2014 Pdk1 controls upstream pi3k expression and pip3 generation. Oncogene 33 3043–3053
Evangelisti C, Florian MC, Massimi I, et al. 2009 Mir-128up-regulation inhibits reelin and dcx expression and reduces neuroblastoma cell motility and invasiveness. FASEB J. 23 4276–4287
Hu J, Cheng Y, Li Y, et al. 2014 Microrna-128 plays a critical role in human non-small cell lung cancer tumorigenesis, angiogenesis and lymphangiogenesis by dirctly targeting vascular endothelial growth factor-c. Eur. J. Cancer 50 2336–2350
Katada T, Ishiguro H, Kuwabara Y, et al. 2009 Microrna expression profile in undifferentiated gastric cancer. Int. J. Oncol. 34 537–542
Kurashige J, Kamohara H, Watanabe M, et al. 2012 Microrna-200b regulates cell proliferation, invasion, and migration by directly targeting zeb2 in gastric carcinoma. Ann. Surg. Oncol. 19 S656–S664
Li M, Fu W, Wo L, et al. 2013 Mir-128 and its target genes in tumorigenesis and metastasis. Exp. Cell Res. 319 3059–3064
Li T, Lu YY, Zhao XD, et al. 2014 Microrna-296-5p increases proliferation in gastric cancer throughrepression of caudal-related homeobox 1. Oncogene 33 783–793
Palumbo T, Faucz FR, Azevedo M, et al. 2013 Functional screen analysis reveals mir-26b and mir-128 as central regulators of pituitary somatomammotrophic tumor growth through activation of the pten-akt pathway. Oncogene 32 1651–1659
Qian P, Banerjee A, Wu ZS, et al. 2012 Loss of snail regulated mir-128-2 on chromosome 3p22.3 targets multiple stem cell factors to promote transformation of mammary epithelial cells. Cancer Res. 72 6036–6050
Raimondi C and Falasca M 2011 Targeting pdk1 in cancer. Curr. Med. Chem. 18 2763–2769
Shen L, Chen XD and Zhang YH 2014 Microrna-128 promotes proliferation in osteosarcoma cells by downregulating pten. Tumour Biol. 35 2069–2074
Siegel R, Ma J, Zou Z, et al. 2014 Cancer statistics, 2014. CA Cancer J. Clin. 64 9–29
Tchernitsa O, Kasajima A, Schafer R, et al. 2010 Systematic evaluation of the mirna-ome and its downstream effects on mrna expression identifies gastric cancer progression. J. Pathol. 222 310–319
Tong F, Cao P, Yin Y, et al. 2014 Micrornas in gastric cancer: from benchtop to bedside. Dig. Dis. Sci. 59 24–30
Tsukamoto Y, Nakada C, Noguchi T, et al. 2010a MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3ζ. Cancer Res. 70 2339–2351
Tsukamoto Y, Nakada C, Noguchi T, et al. 2010b Microrna-375 is downregulated in gastric carcinomas and regulates cell survival by targeting pdk1 and 14-3-3zeta. Cancer Res. 70 2339–2349
Volinia S, Calin GA, Liu CG, et al. 2006 A microrna expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. USA 103 2257–2261
Woo HH, Laszlo CF, Greco S, et al. 2012 Regulation of colony stimulating factor-1 expression and ovarian cancer cell behavior in vitro by mir-128 and mir-152. Mol. Cancer. 11 58
Wu WK, Lee CW, Cho CH, et al. 2010 Microrna dysregulation in gastric cancer: a new player enters the game. Oncogene 29 5761–5771
Xia J, Wu Z, Yu C, et al. 2012 Mir-124 inhibits cell proliferation in gastric cancer through down-regulation of sphk1. J. Pathol. 227 470–480
Yates LA, Norbury CJ and Gilbert RJ 2013 The long and short of microrna. Cell 153 516–519
Yu LL, Dai N, Yu HG, et al. 2010 Akt associates with nuclear factor kappab and plays an important role in chemoresistance of gastric cancer cells. Oncol. Rep. 24 113–119
Zhang Y, Chao T, Li R, et al. 2009 Microrna-128 inhibits glioma cells proliferation by targetingtranscription factor e2f3a. J. Mol. Med. 87 43–51
Zhang BG, Li JF, Yu BQ, et al. 2012 Microrna-21 promotes tumorproliferation and invasion in gastric cancer by targeting pten. Oncol. Rep. 27 1019–1026
Zheng B, Liang L, Wang C, et al. 2011 Microrna-148a suppresses tumor cell invasion and metastasis by downregulating rock1 in gastric cancer. Clin. Cancer Res. 17 7574–7583
Zhou J, Song S, He S, et al. 2014 MicroRNA-375 targets PDK1 in pancreatic carcinoma and suppresses cell growth through the Akt signaling pathway. Int. J. Mol. Med. 33 950–956
Zhu Y, Yu F and Jiao Y 2011 Reduced mir-128 in breast tumor-initiating cells induces chemotherapeutic resistance via bmi-1 and abcc5. Clin. Cancer Res. 17 7105–7115
Author information
Authors and Affiliations
Corresponding author
Additional information
[Zhang L, Lei J, Fang Z-L and Xiong J-P 2016 MiR-128b is down-regulated in gastric cancer and negatively regulates tumour cell viability by targeting PDK1/Akt/NF-κB axis. J. Biosci.] DOI 10.1007/s12038-016-9586-0
Rights and permissions
About this article
Cite this article
Zhang, L., Lei, J., Fang, ZL. et al. MiR-128b is down-regulated in gastric cancer and negatively regulates tumour cell viability by targeting PDK1/Akt/NF-κB axis. J Biosci 41, 77–85 (2016). https://doi.org/10.1007/s12038-016-9586-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12038-016-9586-0