Open Access

MicroRNA-488 inhibits proliferation, invasion and EMT in osteosarcoma cell lines by targeting aquaporin 3

  • Authors:
    • Jing Qiu
    • Yongzhi Zhang
    • Hu Chen
    • Zhi Guo
  • View Affiliations

  • Published online on: July 16, 2018     https://doi.org/10.3892/ijo.2018.4483
  • Pages: 1493-1504
  • Copyright : © Qiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It has been reported that aquaporin 3 (AQP3) expression is associated with the progression of numerous types of cancer and microRNA (miRNA/miR) processing. However, the effects and precise mechanisms of AQP3 in osteosarcoma (OS) have not been fully elucidated. The present study aimed to investigate the interaction between AQP3 and miR‑488 in OS. The reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) assay was performed to detect the levels of AQP3 and miR‑488 in OS tissues and cell lines, respectively. Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were detected to analyze the biological functions of miR‑488 and AQP3 in OS cells. Furthermore, mRNA and protein levels of AQP3 was measured by RT‑qPCR and western blot analysis. Furthermore, AQP3 was validated as an miR‑488 target using luciferase assays in OS cells. The present study revealed that the miR‑488 level was significantly downregulated in OS tissues and cell lines, and that the expression of AQP3 was markedly increased. Notable, the low miR‑488 expression level was associated with upregulated AQP3 expression in OS tissues. Furthermore, introduction of miR‑488 markedly suppressed the proliferation, invasion and EMT of OS cells. However, miR‑488-knockdown increased the proliferation, invasion and EMT of OS cells. The present study demonstrated that miR‑488 could directly target AQP3 using bioinformatics analysis and luciferase reporter assays. In addition, AQP3-silencing had similar effects to miR‑488 overexpression on OS cells. Overexpression of AQP3 in OS cells partially reversed the inhibitory effects of miR‑488 mimic. miR‑488 inhibited the proliferation, invasion and EMT of OS cells by directly downregulating AQP3 expression, and miR‑488 targeting AQP3 was responsible for inhibition of the proliferation, invasion and EMT of OS cells.

References

1 

Yang J and Zhang W: New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 25:398–406. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Siegel HJ and Pressey JG: Current concepts on the surgical and medical management of osteosarcoma. Expert Rev Anticancer Ther. 8:1257–1269. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Chen L, Wang Q, Wang GD, Wang HS, Huang Y, Liu XM and Cai XH: miR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2 pathway in osteosarcoma. FEBS Lett. 587:1366–1372. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Mirabello L, Troisi RJ and Savage SA: Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the Surveillance, Epidemiology, and End Results Program. Cancer. 115:1531–1543. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Parisi M, Amodeo G, Capurro C, Dorr R, Ford P and Toriano R: Biophysical properties of epithelial water channels. Biophys Chem. 68:255–263. 1997. View Article : Google Scholar

6 

Agre P: The aquaporin water channels. Proc Am Thorac Soc. 3:5–13. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Rojek AM, Skowronski MT, Füchtbauer EM, Füchtbauer AC, Fenton RA, Agre P, Frøkiaer J and Nielsen S: Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice. Proc Natl Acad Sci USA. 104:3609–3614. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Hoque MO, Soria JC, Woo J, Lee T, Lee J, Jang SJ, Upadhyay S, Trink B, Monitto C, Desmaze C, et al: Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth. Am J Pathol. 168:1345–1353. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Liu W, Wang K, Gong K, Li X and Luo K: Epidermal growth factor enhances MPC-83 pancreatic cancer cell migration through the upregulation of aquaporin 3. Mol Med Rep. 6:607–610. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Ismail M, Bokaee S, Morgan R, Davies J, Harrington KJ and Pandha H: Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy. Br J Cancer. 100:1889–1895. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Nico B, Annese T, Tamma R, Longo V, Ruggieri S, Senetta R, Cassoni P, Specchia G, Vacca A and Ribatti D: Aquaporin-4 expression in primary human central nervous system lymphomas correlates with tumour cell proliferation and phenotypic heterogeneity of the vessel wall. Eur J Cancer. 48:772–781. 2012. View Article : Google Scholar

12 

Chae YK, Kang SK, Kim MS, Woo J, Lee J, Chang S, Kim DW, Kim M, Park S, Kim I, et al: Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML). PLoS One. 3:e25942008. View Article : Google Scholar : PubMed/NCBI

13 

Chae YK, Woo J, Kim MJ, Kang SK, Kim MS, Lee J, Lee SK, Gong G, Kim YH, Soria JC, et al: Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non small cell lung cancer. PLoS One. 3:e21622008. View Article : Google Scholar : PubMed/NCBI

14 

Kang SK, Chae YK, Woo J, Kim MS, Park JC, Lee J, Soria JC, Jang SJ, Sidransky D and Moon C: Role of human aquaporin 5 in colorectal carcinogenesis. Am J Pathol. 173:518–525. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Mei Q, Li X, Guo M, Fu X and Han W: The miRNA network: Micro-regulator of cell signaling in cancer. Expert Rev Anticancer Ther. 14:1515–1527. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Kloosterman WP and Plasterk RH: The diverse functions of microRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Yan W, Qian L, Chen J, Chen W and Shen B: Comparison of prognostic microRNA biomarkers in blood and tissues for gastric cancer. J Cancer. 7:95–106. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Mao B and Wang G: MicroRNAs involved with hepatocellular carcinoma (review). Oncol Rep. 34:2811–2820. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Wang J, Yang M, Li Y and Han B: The role of microRNAs in the chemoresistance of breast cancer. Drug Dev Res. 76:368–374. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Hollis M, Nair K, Vyas A, Chaturvedi LS, Gambhir S and Vyas D: MicroRNAs potential utility in colon cancer: Early detection, prognosis, and chemosensitivity. World J Gastroenterol. 21:8284–8292. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Liu Y, Li Y, Liu J, Wu Y and Zhu Q: MicroRNA-132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4. Int J Oncol. 47:1672–1684. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Cheng DD, Yu T, Hu T, Yao M, Fan CY and Yang QC: miR-542 5p is a negative prognostic factor and promotes osteosarcoma tumorigenesis by targeting HUWE1. Oncotarget. 6:42761–42772. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔC(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

24 

Zeng Z and Zhu BH: Arnebin-1 promotes the angiogenesis of human umbilical vein endothelial cells and accelerates the wound healing process in diabetic rats. J Ethnopharmacol. 154:653–662. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Ottaviani G and Jaffe N: The etiology of osteosarcoma. Cancer Treat Res. 152:15–32. 2009. View Article : Google Scholar

26 

Chen J, Wang T, Zhou YC, Gao F, Zhang ZH, Xu H, Wang SL and Shen LZ: Aquaporin 3 promotes epithelial-mesenchymal transition in gastric cancer. J Exp Clin Cancer Res. 33:382014. View Article : Google Scholar : PubMed/NCBI

27 

Kusayama M, Wada K, Nagata M, Ishimoto S, Takahashi H, Yoneda M, Nakajima A, Okura M, Kogo M and Kamisaki Y: Critical role of aquaporin 3 on growth of human esophageal and oral squamous cell carcinoma. Cancer Sci. 102:1128–1136. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Hou SY, Li YP, Wang JH, Yang SL, Wang Y, Wang Y and Kuang Y: Aquaporin-3 inhibition reduces the growth of NSCLC cells induced by hypoxia. Cell Physiol Biochem. 38:129–140. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Li A, Lu D, Zhang Y, Li J, Fang Y, Li F and Sun J: Critical role of aquaporin-3 in epidermal growth factor-induced migration of colorectal carcinoma cells and its clinical significance. Oncol Rep. 29:535–540. 2013. View Article : Google Scholar

30 

Satooka H and Hara-Chikuma M: Aquaporin-3 controls breast cancer cell migration by regulating hydrogen peroxide transport and its downstream cell sgnaling. Mol Cell Biol. 36:1206–1218. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Guo X, Sun T, Yang M, Li Z, Li Z and Gao Y: Prognostic value of combined aquaporin 3 and aquaporin 5 overexpression in hepatocellular carcinoma. BioMed Res Int. 2013:2065252013. View Article : Google Scholar : PubMed/NCBI

32 

Huang X, Huang L and Shao M: Aquaporin 3 facilitates tumor growth in pancreatic cancer by modulating mTOR signaling. Biochem Biophys Res Commun. 486:1097–1102. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Liu YL, Matsuzaki T, Nakazawa T, Murata S, Nakamura N, Kondo T, Iwashina M, Mochizuki K, Yamane T, Takata K, et al: Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. Hum Pathol. 38:171–178. 2007. View Article : Google Scholar

34 

Chen J, Wang Z, Xu D, Liu Y and Gao Y: Aquaporin 3 promotes prostate cancer cell motility and invasion via extracellular signal-regulated kinase 1/2-mediated matrix metalloproteinase-3 secretion. Mol Med Rep. 11:2882–2888. 2015. View Article : Google Scholar

35 

Direito I, Paulino J, Vigia E, Brito MA and Soveral G: Differential expression of aquaporin-3 and aquaporin-5 in pancreatic ductal adenocarcinoma. J Surg Oncol. 115:980–996. 2017. View Article : Google Scholar : PubMed/NCBI

36 

Osada H and Takahashi T: MicroRNAs in biological processes and carcinogenesis. Carcinogenesis. 28:2–12. 2007. View Article : Google Scholar

37 

Zhang B, Pan X, Cobb GP and Anderson TA: MicroRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar

38 

Sikand K, Slaibi JE, Singh R, Slane SD and Shukla GC: miR 488* inhibits androgen receptor expression in prostate carcinoma cells. Int J Cancer. 129:810–819. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Yang Z, Feng Z, Gu J, Li X, Dong Q, Liu K, Li Y and OuYang L: microRNA-488 inhibits chemoresistance of ovarian cancer cells by targeting Six1 and mitochondrial function. Oncotarget. 8:80981–80993. 2017.PubMed/NCBI

40 

Lv Y, Shi Y, Han Q and Dai G: Histone demethylase PHF8 accelerates the progression of colorectal cancer and can be regulated by miR-488 in vitro. Mol Med Rep. 16:4437–4444. 2017. View Article : Google Scholar : PubMed/NCBI

41 

Hu D, Shen D, Zhang M, Jiang N, Sun F, Yuan S and Wan K: miR-488 suppresses cell proliferation and invasion by targeting ADAM9 and lncRNA HULC in hepatocellular carcinoma. Am J Cancer Res. 7:2070–2080. 2017.PubMed/NCBI

42 

Fang C, Chen YX, Wu NY, Yin JY, Li XP, Huang HS, Zhang W, Zhou HH and Liu ZQ: miR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway. Sci Rep. 7:403842017. View Article : Google Scholar : PubMed/NCBI

43 

Zhao Y, Lu G, Ke X, Lu X, Wang X, Li H, Ren M and He S: miR-488 acts as a tumor suppressor gene in gastric cancer. Tumour Biol. 37:8691–8698. 2016. View Article : Google Scholar : PubMed/NCBI

44 

Simpson-Haidaris PJ and Rybarczyk B: Tumors and fibrinogen. The role of fibrinogen as an extracellular matrix protein. Ann N Y Acad Sci. 936:406–425. 2001. View Article : Google Scholar : PubMed/NCBI

45 

Bogenrieder T and Herlyn M: Axis of evil: Molecular mechanisms of cancer metastasis. Oncogene. 22:6524–6536. 2003. View Article : Google Scholar : PubMed/NCBI

46 

Vihinen P and Kähäri VM: Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets. Int J Cancer. 99:157–166. 2002. View Article : Google Scholar : PubMed/NCBI

47 

Sounni NE, Janssen M, Foidart JM and Noel A: Membrane type-1 matrix metalloproteinase and TIMP-2 in tumor angiogenesis. Matrix Biol. 22:55–61. 2003. View Article : Google Scholar : PubMed/NCBI

48 

Hornebeck W, Emonard H, Monboisse JC and Bellon G: Matrix-directed regulation of pericellular proteolysis and tumor progression. Semin Cancer Biol. 12:231–241. 2002. View Article : Google Scholar : PubMed/NCBI

49 

Klein G, Vellenga E, Fraaije MW, Kamps WA and de Bont ES: The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol. 50:87–100. 2004. View Article : Google Scholar : PubMed/NCBI

50 

Herszényi L, Hritz I, Lakatos G, Varga MZ and Tulassay Z: The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci. 13:13240–13263. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Guarino M: Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol. 39:2153–2160. 2007. View Article : Google Scholar : PubMed/NCBI

52 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

53 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

54 

Jiang B, Li Z, Zhang W, Wang H, Zhi X, Feng J, Chen Z, Zhu Y, Yang L, Xu H, et al: miR-874 Inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer. J Gastroenterol. 49:1011–1025. 2014. View Article : Google Scholar

Related Articles

Journal Cover

October 2018
Volume 53 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Qiu, J., Zhang, Y., Chen, H., & Guo, Z. (2018). MicroRNA-488 inhibits proliferation, invasion and EMT in osteosarcoma cell lines by targeting aquaporin 3. International Journal of Oncology, 53, 1493-1504. https://doi.org/10.3892/ijo.2018.4483
MLA
Qiu, J., Zhang, Y., Chen, H., Guo, Z."MicroRNA-488 inhibits proliferation, invasion and EMT in osteosarcoma cell lines by targeting aquaporin 3". International Journal of Oncology 53.4 (2018): 1493-1504.
Chicago
Qiu, J., Zhang, Y., Chen, H., Guo, Z."MicroRNA-488 inhibits proliferation, invasion and EMT in osteosarcoma cell lines by targeting aquaporin 3". International Journal of Oncology 53, no. 4 (2018): 1493-1504. https://doi.org/10.3892/ijo.2018.4483