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Article

miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer

  • Authors:
    • Dongli Zhao
    • Yanxia Sui
    • Xiaoqiang Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 1075-1082
    |
    Published online on: November 26, 2015
       https://doi.org/10.3892/or.2015.4450
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Abstract

MicroRNAs (miRNAs) regulate cell proliferation, apoptosis and carcinogenesis by targeting related mRNAs in different types of cancer. miR-331-3p has been found to regulate the development and progression of various types of cancer cells. However, little research has been conducted on the role of miR-331-3p in colorectal cancer (CRC). The present study aimed to explore the function of miR-331-3p in CRC. We found that miR-331-3p was significantly downregulated in CRC tissues and cells compared to the level in healthy colon tissues and cells. Overexpression of miR-331-3p by transfection with pre‑miR-331-3p inhibited cell proliferation, promoted apoptosis and activated caspase-3. Furthermore, the protein expression level of apoptosis-related protein Bcl-2 was downregulated and Bax was upregulated by pre‑miR‑331-3p. Downregulation of the expression of miR-331-3p by transfection with AS-miR-331-3p had the opposite effect. Moreover, we found that HER2 was overexpressed in the CRC cell lines, and the expression level of HER2 was negatively regulated by miR‑331-3p. Additionally, knockdown of HER2 inhibited cell proliferation and phosphorylation of Akt and ERK1/2 induced by AS-miR-331-3p. Overall, we identified that miR‑331-3p is underexpressed in CRC and contributes to cell growth regulation by targeting HER2 through activating the PI3K/Akt and ERK1/2 signaling pathways.
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View References

1 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Ferrari P, Jenab M, Norat T, Moskal A, Slimani N, Olsen A, Tjønneland A, Overvad K, Jensen MK, Boutron-Ruault MC, et al: Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 121:2065–2072. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN, Jemal A, Schymura MJ, Lansdorp-Vogelaar I, Seeff LC, et al: Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 116:544–573. 2010. View Article : Google Scholar

5 

Bosetti C, Levi F, Rosato V, Bertuccio P, Lucchini F, Negri E and La Vecchia C: Recent trends in colorectal cancer mortality in Europe. Int J Cancer. 129:180–191. 2011. View Article : Google Scholar

6 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, et al: Frequent deletions and downregulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 99:15524–15529. 2002. View Article : Google Scholar

8 

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Singh SR and Rameshwar P: MicroRNA in Development and in the Progression of Cancer. Springer; New York, NY: 2014, View Article : Google Scholar

11 

Wang S, Xiang J, Li Z, Lu S, Hu J, Gao X, Yu L, Wang L, Wang J, Wu Y, et al: A plasma microRNA panel for early detection of colorectal cancer. Int J Cancer. 136:152–161. 2015. View Article : Google Scholar

12 

Wang L, Tang H, Thayanithy V, Subramanian S, Oberg AL, Cunningham JM, Cerhan JR, Steer CJ and Thibodeau SN: Gene networks and microRNAs implicated in aggressive prostate cancer. Cancer Res. 69:9490–9497. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Zanette DL, Rivadavia F, Molfetta GA, Barbuzano FG, Proto-Siqueira R, Silva-Jr WA, Falcão RP and Zago MA: miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res. 40:1435–1440. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Nymark P, Guled M, Borze I, Faisal A, Lahti L, Salmenkivi K, Kettunen E, Anttila S and Knuutila S: Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos- and histology-related changes in lung cancer. Genes Chromosomes. Cancer. 50:585–597. 2011.

15 

Epis MR, Giles KM, Candy PA, Webster RJ and Leedman PJ: miR-331-3p regulates expression of neuropilin-2 in glioblastoma. J Neurooncol. 116:67–75. 2014. View Article : Google Scholar :

16 

Guo X, Guo L, Ji J, Zhang J, Zhang J, Chen X, Cai Q, Li J, Gu Q, Liu B, et al: miRNA-331-3p directly targets E2F1 and induces growth arrest in human gastric cancer. Biochem Biophys Res Commun. 398:1–6. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Epis MR, Giles KM, Kalinowski FC, Barker A, Cohen RJ and Leedman PJ: Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells. J Biol Chem. 287:35251–35259. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Epis MR, Giles KM, Barker A, Kendrick TS and Leedman PJ: miR-331-3p regulates ERBB-2 expression and androgen receptor signaling in prostate cancer. J Biol Chem. 284:24696–24704. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Kruser TJ and Wheeler DL: Mechanisms of resistance to HER family targeting antibodies. Exp Cell Res. 316:1083–1100. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Mass RD: The HER receptor family: A rich target for therapeutic development. Int J Radiat Oncol Biol Phys. 58:932–940. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Holbro T and Hynes NE: ErbB receptors: Directing key signaling networks throughout life. Annu Rev Pharmacol Toxicol. 44:195–217. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Marmor MD, Skaria KB and Yarden Y: Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys. 58:903–913. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 235:177–182. 1987. View Article : Google Scholar : PubMed/NCBI

24 

Yu D and Hung MC: Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene. 19:6115–6121. 2000. View Article : Google Scholar

25 

Tan M, Yao J and Yu D: Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. Cancer Res. 57:1199–1205. 1997.PubMed/NCBI

26 

Yu D, Jing T, Liu B, Yao J, Tan M, McDonnell TJ and Hung MC: Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol Cell. 2:581–591. 1998. View Article : Google Scholar : PubMed/NCBI

27 

Blok EJ, Kuppen PJ, van Leeuwen JE and Sier CF: Cytoplasmic overexpression of HER2: A key factor in colorectal cancer. Clin Med Insights Oncol. 7:41–51. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Li SS, Buchbinder E, Wu L, Bjorge JD, Fujita DJ and Zhu S: EGFR and HER2 levels are frequently elevated in colon cancer cells. Discoveries Rep. 1:e12014. View Article : Google Scholar

30 

Hynes NE and MacDonald G: ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 21:177–184. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Nahta R and O'Regan RM: Evolving strategies for overcoming resistance to HER2-directed therapy: Targeting the PI3K/Akt/mTOR pathway. Clin Breast Cancer. 10(Suppl 3): S72–S78. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Citri A and Yarden Y: EGF-ERBB signalling: Towards the systems level. Nat Rev Mol Cell Biol. 7:505–516. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Chen CZ: MicroRNAs as oncogenes and tumor suppressors. N Engl J Med. 353:1768–1771. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H, Sugihara K and Mori M: Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 34:1069–1075. 2009.PubMed/NCBI

35 

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Epis MR, Barker A, Giles KM, Beveridge DJ and Leedman PJ: The RNA-binding protein HuR opposes the repression of ERBB-2 gene expression by microRNA miR-331-3p in prostate cancer cells. J Biol Chem. 286:41442–41454. 2011. View Article : Google Scholar : PubMed/NCBI

38 

Chang RM, Yang H, Fang F, Xu JF and Yang LY: MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase. Hepatology. 60:1251–1263. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Kafi SG, Lari S and Nassiri G: HER2/neu expression in colon adenocarcinoma and its correlation with clinicopathologic variables. IJBMS. 9:64–69. 2006.

40 

Kim SY, Kim HP, Kim YJ, Oh Y, Im SA, Lee D, Jong HS, Kim TY and Bang YJ: Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin. Int J Oncol. 32:89–95. 2008.

41 

Mebratu Y and Tesfaigzi Y: How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle. 8:1168–1175. 2009. View Article : Google Scholar : PubMed/NCBI

42 

Ross JS and McKenna BJ: The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 19:554–568. 2001. View Article : Google Scholar : PubMed/NCBI

43 

Yarden Y and Sliwkowski MX: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2:127–137. 2001. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhao D, Sui Y and Zheng X: miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer. Oncol Rep 35: 1075-1082, 2016.
APA
Zhao, D., Sui, Y., & Zheng, X. (2016). miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer. Oncology Reports, 35, 1075-1082. https://doi.org/10.3892/or.2015.4450
MLA
Zhao, D., Sui, Y., Zheng, X."miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer". Oncology Reports 35.2 (2016): 1075-1082.
Chicago
Zhao, D., Sui, Y., Zheng, X."miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer". Oncology Reports 35, no. 2 (2016): 1075-1082. https://doi.org/10.3892/or.2015.4450
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao D, Sui Y and Zheng X: miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer. Oncol Rep 35: 1075-1082, 2016.
APA
Zhao, D., Sui, Y., & Zheng, X. (2016). miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer. Oncology Reports, 35, 1075-1082. https://doi.org/10.3892/or.2015.4450
MLA
Zhao, D., Sui, Y., Zheng, X."miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer". Oncology Reports 35.2 (2016): 1075-1082.
Chicago
Zhao, D., Sui, Y., Zheng, X."miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer". Oncology Reports 35, no. 2 (2016): 1075-1082. https://doi.org/10.3892/or.2015.4450
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