miR‑338‑3p inhibits A549 lung cancer cell proliferation and invasion by targeting AKT and β‑catenin signaling pathways

Liu,Jia; Cao,Linggai; Zhao,Na; Feng,Yue; Yu,Ze; Li,Yuhua; Teng,Chunbo; Hu,Jifan; Li,Tao

doi:10.3892/mmr.2019.10215

miR‑338‑3p inhibits A549 lung cancer cell proliferation and invasion by targeting AKT and β‑catenin signaling pathways

Authors:
- Jia Liu
- Linggai Cao
- Na Zhao
- Yue Feng
- Ze Yu
- Yuhua Li
- Chunbo Teng
- Jifan Hu
- Tao Li
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Affiliations: Department of Genetics, College of Life Science, Northeast Forestry University, Harbin, Heilongjiang 150040, P.R. China, Department of Basic Science, Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94305, USA
Published online on: May 9, 2019 https://doi.org/10.3892/mmr.2019.10215
Pages: 33-40
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the underlying mechanism of microRNA‑338‑3p (miR‑338‑3p) in lung cancer cell (A549) invasion and proliferation. A microarray assay showed that miR‑338‑3p upregulated 216 and downregulated 147 genes in A549 cells, and the differentially expressed genes were enriched for several signaling pathways, including AKT and β‑catenin signaling pathways. Western blotting results showed that phosphorylated (p)‑AKT at Ser473 and at Thr308 and p‑β‑catenin at Ser552 were downregulated. Inhibiting AKT signaling pathway decreased β‑catenin signaling pathway. Overexpression of β‑catenin promoted the invasion of A549 cells. In addition, miR‑338‑3p showed inhibitory effect on the primary tumor developed from KrasG12D mice. Together, the data of the present study support that miR‑338‑3p inhibits lung cancer cell invasion and proliferation by downregulating AKT/β‑catenin signaling pathway. The present findings supported the potential use of miR‑338‑3p in the treatment of lung cancer.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 62:283–298. 2012. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al: Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 62:220–241. 2012. View Article : Google Scholar : PubMed/NCBI
3	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
4	Wang X and Adjei AA: Lung cancer and metastasis: New opportunities and challenges. Cancer Metastasis Rev. 34:169–171. 2015. View Article : Google Scholar : PubMed/NCBI
5	Catela Ivkovic T, Voss G, Cornelia H and Ceder Y: microRNAs as cancer therapeutics: A step closer to clinical application. Cancer Lett. 407:113–122. 2017. View Article : Google Scholar : PubMed/NCBI
6	Chen X, Pan M, Han LL, Lu HT, Hao XW and Dong Q: miR-338-3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a. FEBS Lett. 587:3729–3737. 2013. View Article : Google Scholar : PubMed/NCBI
7	Baek SH, Ko JH, Lee JH, Kim C, Lee H, Nam D, Lee J, Lee SG, Yang WM, Um JY, et al: Ginkgolic acid inhibits invasion and migration and TGF-β-induced EMT of lung cancer cells through PI3K/Akt/mTOR inactivation. J Cell Physiol. 232:346–354. 2017. View Article : Google Scholar : PubMed/NCBI
8	Jiao D, Wang J, Lu W, Tang X, Chen J, Mou H and Chen QY: Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-Met dependent PI3K/Akt/mTOR signaling pathways in lung cancer. Mol Ther Oncolytics. 3:160182016. View Article : Google Scholar : PubMed/NCBI
9	Meng J, Zhang XT, Liu XL, Fan L, Li C, Sun Y, Liang XH, Wang JB, Mei QB, Zhang F and Zhang T: WSTF promotes proliferation and invasion of lung cancer cells by inducing EMT via PI3K/Akt and IL-6/STAT3 signaling pathways. Cell Signal. 28:1673–1682. 2016. View Article : Google Scholar : PubMed/NCBI
10	Pan H, Jiang T, Cheng N, Wang Q, Ren S, Li X, Zhao C, Zhang L, Cai W and Zhou C: Long non-coding RNA BC087858 induces non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT in non-small-cell lung cancer. Oncotarget. 7:49948–49960. 2016. View Article : Google Scholar : PubMed/NCBI
11	Hong-Yuan W and Xiao-Ping C: miR-338-3p suppresses epithelial-mesenchymal transition and metastasis in human nonsmall cell lung cancer. Indian J Cancer. 52 (Suppl 3):E168–E171. 2015. View Article : Google Scholar : PubMed/NCBI
12	Zhang G, Zheng H, Zhang G, Cheng R, Lu C, Guo Y and Zhao G: MicroRNA-338-3p suppresses cell proliferation and induces apoptosis of non-small-cell lung cancer by targeting sphingosine kinase 2. Cancer Cell Int. 17:462017. View Article : Google Scholar : PubMed/NCBI
13	Bos JL: Ras oncogenes in human cancer: A review. Cancer Res. 49:4682–4689. 1989.PubMed/NCBI
14	Avruch J, Zhang XF and Kyriakis JM: Raf meets Ras: Completing the framework of a signal-transduction pathway. Trends Biochem Sci. 19:279–283. 1994. View Article : Google Scholar : PubMed/NCBI
15	Khosravi-Far R and Der CJ: The Ras signal-transduction pathway. Cancer Metastasis Rev. 13:67–89. 1994. View Article : Google Scholar : PubMed/NCBI
16	Mills NE, Fishman CL, Rom WN, Dubin N and Jacobson DR: Increased prevalence of K-Ras oncogene mutations in lung adenocarcinoma. Cancer Res. 55:1444–1447. 1995.PubMed/NCBI
17	Pellegata NS, Sessa F, Renault B, Bonato M, Leone BE, Solcia E and Ranzani GN: K-Ras and P53 gene-mutations in pancreatic-cancer: Ductal and nonductal tumors progress through different genetic lesions. Cancer Res. 54:1556–1560. 1994.PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T and Tuveson DA: Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Gene Dev. 15:3243–3248. 2001. View Article : Google Scholar : PubMed/NCBI
20	Cai CL, Xie YX, Wu LL, Chen XJ, Liu HM, Zhou Y, Zou H, Liu D, Zhao Y, Kong X and Liu P: PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma. Sci Rep. 7:462502017. View Article : Google Scholar : PubMed/NCBI
21	Tamura T, Kurishima K, Nakazawa K, Kagohashi K, Ishikawa H, Satoh H and Hizawa N: Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol. 3:217–221. 2015. View Article : Google Scholar : PubMed/NCBI
22	Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T and Dive C: Progress and prospects of early detection in lung cancer. Open Biol. 7:1700702017. View Article : Google Scholar : PubMed/NCBI
23	Lemjabbar-Alaoui H, Hassan OU, Yang YW and Buchanan P: Lung cancer: Biology and treatment options. Biochim Biophys Acta. 1856:189–210. 2015.PubMed/NCBI
24	Tsai JH and Yang J: Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 27:2192–2206. 2013. View Article : Google Scholar : PubMed/NCBI
25	Shibue T and Weinberg RA: EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat Rev Clin Oncol. 14:611–629. 2017. View Article : Google Scholar : PubMed/NCBI
26	Linnerth-Petrik NM, Santry LA, Moorehead R, Jücker M, Wootton SK and Petrik J: Akt isoform specific effects in ovarian cancer progression. Oncotarget. 7:74820–74833. 2016. View Article : Google Scholar : PubMed/NCBI
27	Mundi PS, Sachdev J, McCourt C and Kalinsky K: AKT in cancer: New molecular insights and advances in drug development. Br J Clin Pharmacol. 82:943–956. 2016. View Article : Google Scholar : PubMed/NCBI
28	Tanno S, Tanno S, Mitsuuchi Y, Altomare DA, Xiao GH and Testa JR: AKT activation up-regulates insulin-like growth factor I receptor expression and promotes invasiveness of human pancreatic cancer cells. Cancer Res. 61:589–593. 2001.PubMed/NCBI
29	Han J, Zhang L, Zhang J, Jiang Q, Tong D, Wang X, Gao X, Zhao L and Huang C: CREBRF promotes the proliferation of human gastric cancer cells via the AKT signaling pathway. Cell Mol Biol (Noisy-le-grand). 64:40–45. 2018. View Article : Google Scholar : PubMed/NCBI
30	Enomoto A, Murakami H, Asai N, Morone N, Watanabe T, Kawai K, Murakumo Y, Usukura J, Kaibuchi K and Takahashi M: Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev Cell. 9:389–402. 2005. View Article : Google Scholar : PubMed/NCBI