miR‑379‑5p inhibits cell proliferation and promotes cell apoptosis in non‑small cell lung cancer by targeting β‑arrestin‑1

Jiang,Yonghong; Zhu,Panpan; Gao,Yamei; Wang,Aiping

doi:10.3892/mmr.2020.11553

miR‑379‑5p inhibits cell proliferation and promotes cell apoptosis in non‑small cell lung cancer by targeting β‑arrestin‑1

Authors:
- Yonghong Jiang
- Panpan Zhu
- Yamei Gao
- Aiping Wang
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Affiliations: Department of Second Inpatient Area of Oncology Surgery, Weinan Central Hospital, Weinan, Shaanxi 714000, P.R. China, Department of Second Inpatient Area of Oncology Surgery, Weinan Central Hospital, Weinan, Shaanxi 714000, P.R. China, Department of Nursing, Weinan Central Hospital, Weinan, Shaanxi 714000, P.R. China
Published online on: September 30, 2020 https://doi.org/10.3892/mmr.2020.11553
Pages: 4499-4508
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer is the most common fatal type of cancer, demonstrating high incidence rates in both sexes. Therefore, it is of vital importance to devise more effective and targeted therapies to improve the treatment quality for patients. The present study aimed to determine the effects of microRNA (miR)‑379‑5p on cell proliferation and apoptosis, in addition to its underlying molecular mechanisms in lung cancer. Tumor and adjacent normal tissues were obtained from patients with NSCLC and transfection experiments in A549 cells were performed using miR‑379‑5p mimics and pcDNA3.1‑ β‑arrestin‑1 (ARRB1) overexpression plasmids. The cell proliferation rate was determined using a Cell Counting Kit‑8 assay and the cell apoptotic rate was analyzed using flow cytometry. Additionally, the mRNA and protein expression levels of proliferation‑related signaling (PI3K, p‑PI3K, AKT and p‑AKT) and apoptotic‑related factors (Bcl‑2, Bax and caspase‑3) were detected using reverse transcription‑quantitative PCR and western blotting, respectively. The results of the present study revealed that miR‑379‑5p expression levels were downregulated, whereas ARRB1 expression levels were significantly upregulated in NSCLC tissues and cell lines. Following the successful transfection of the miR‑379‑5p mimic and ARRB1 overexpression plasmid, it was revealed that the overexpression of miR‑379‑5p inhibited cell proliferation and promoted cell apoptosis, whereas ARRB1 overexpression reversed this inhibition over proliferation and promotion of apoptosis. The increased cell apoptotic rate observed in the miR‑379‑5p mimics group was associated with a significant downregulation and upregulation of Bcl‑2, and Bax and caspase‑3 expression levels, respectively. Finally, ARRB1 was identified as a target gene of miR‑379‑5p. In conclusion, the expression levels of miR‑379‑5p were demonstrated to be significantly downregulated in lung cancer. In addition, miR‑379‑5p overexpression led to the decreased expression levels of Bcl‑2, phosphorylated (p)‑PI3K/PI3K and p‑AKT/AKT, and the increased expression levels of Bax and caspase‑3. Overall, this resulted in the inhibition of cell proliferation and promoted cell apoptosis by directly targeting ARRB1. Therefore, miR‑379‑5p may be a potential target for NSCLC treatment due to its ability to inhibit cell proliferation and accelerate the apoptotic process.

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1	Chen R, Xia W, Wang S, Xu Y, Ma Z, Xu W, Zhang E, Wang J, Fang T, Zhang Q, et al: Long noncoding RNA SBF2-AS1 is critical for tumorigenesis of early-stage lung adenocarcinoma. Mol Ther Nucleic Acids. 16:543–553. 2019. View Article : Google Scholar : PubMed/NCBI
2	Nanavaty P, Alvarez MS and Alberts WM: Lung cancer screening: Advantages, controversies, and applications. Cancer Control. 21:9–14. 2014. View Article : Google Scholar : PubMed/NCBI
3	Richtmann S, Wilkens D, Warth A, Lasitschka F, Winter H, Christopoulos P, Herth FJF, Muley T, Meister M and Schneider MA: FAM83A and FAM83B as prognostic biomarkers and potential new therapeutic targets in NSCLC. Cancers (Basel). 11:6522019. View Article : Google Scholar
4	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
5	Zhang T, Song X, Liao X, Wang X, Zhu G, Yang C and Xie X: Distinct prognostic values of phospholipase C beta family members for non-small cell lung carcinoma. Biomed Res Int. 2019:42565242019.PubMed/NCBI
6	Castellanos-Rizaldos E, Zhang X, Tadigotla VR, Grimm DG, Karlovich C, Raez LE and Skog JK: Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients. Oncotarget. 10:2911–2920. 2019. View Article : Google Scholar : PubMed/NCBI
7	Liu C, Hu Q, Xu B, Hu X, Su H, Li Q, Zhang X, Yue J and Yu J: Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: Predictors of early tumor response. Cancer. Cell Int. 19:1212019. View Article : Google Scholar
8	Hammond SM: An overview of microRNAs. Adv Drug Deliv Rev. 87:3–14. 2015. View Article : Google Scholar : PubMed/NCBI
9	Di Leva G, Garofalo M and Croce CM: MicroRNAs in cancer. Annu Rev Pathol. 9:287–314. 2014. View Article : Google Scholar : PubMed/NCBI
10	Gebert LFR and MacRae IJ: Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. 20:21–37. 2019. View Article : Google Scholar : PubMed/NCBI
11	Liu B, Li J and Cairns MJ: Identifying miRNAs, targets and functions. Brief Bioinform. 15:1–19. 2014. View Article : Google Scholar : PubMed/NCBI
12	Cazzoli R, Buttitta F, Nicola MD, Malatesta S, Marchetti A, Rom WN and Pass HI: Micrornas derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 8:1156–1162. 2013. View Article : Google Scholar : PubMed/NCBI
13	Wang S, Wang Z, Wang Q, Cui Y and Luo S: Clinical significance of the expression of miRNA-21, miRNA-31 and miRNA-let7 in patients with lung cancer. Saudi J Biol Sci. 26:777–781. 2019. View Article : Google Scholar : PubMed/NCBI
14	Zhao X and Chu J: MicroRNA-379 suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma by targeting tumor protein D52. Exp Ther Med. 16:1232–1240. 2018.PubMed/NCBI
15	Wu D, Niu X, Tao J, Li P, Lu Q, Xu A, Chen W and Wang Z: MicroRNA-379-5p plays a tumor-suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2. Oncol Rep. 37:3502–3508. 2017. View Article : Google Scholar : PubMed/NCBI
16	Xie X, Li YS, Xiao WF, Deng ZH, He HB, Liu Q and Luo W: MicroRNA-379 inhibits the proliferation, migration and invasion of human osteosarcoma cells by targetting EIF4G2. Biosci Rep. 37:BSR201605422017. View Article : Google Scholar : PubMed/NCBI
17	Hao GJ, Hao HJ, Ding YH, Wen H, Li XF, Wang QR and Zhang BB: Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in non-small cell lung cancer cells. FEBS Lett. 591:636–645. 2017. View Article : Google Scholar : PubMed/NCBI
18	Sun JC, Liu B, Zhang RW, Jiao PL, Tan X, Wang YK and Wang WZ: Overexpression of ß-arrestin1 in the rostral ventrolateral medulla downregulates angiotensin receptor and lowers blood pressure in hypertension. Front Physiol. 9:2972018. View Article : Google Scholar : PubMed/NCBI
19	Kim J, Grotegut CA, Wisler JW, Li T, Mao L, Chen M, Chen W, Rosenberg PB, Rockman HA and Lefkowitz RJ: β-Arrestin 1 regulates β2-adrenergic receptor-mediated skeletal muscle hypertrophy and contractility. Skelet Muscle. 8:392018. View Article : Google Scholar : PubMed/NCBI
20	Rosanò L and Bagnato A: β-arrestin1 at the cross-road of endothelin-1 signaling in cancer. J Exp Clin Cancer Res. 35:1212016. View Article : Google Scholar : PubMed/NCBI
21	Lan T, Wang H, Zhang Z, Zhang M, Qu Y, Zhao Z, Fan X, Zhan Q, Song Y and Yu C: Downregulation of β-arrestin 1 suppresses glioblastoma cell malignant progression via inhibition of src signaling. Exp Cell Res. 357:51–58. 2017. View Article : Google Scholar : PubMed/NCBI
22	Dasgupta P, Rizwani W, Pillai S, Davis R, Banerjee S, Hug K, Lloyd M, Coppola D, Haura E and Chellappan SP: ARRB1-mediated regulation of E2F target genes in nicotine-induced growth of lung tumors. J Natl Cancer Inst. 103:317–333. 2011. View Article : Google Scholar : PubMed/NCBI
23	Shen H, Wang L, Zhang J, Dong W, Zhang T, Ni Y, Cao H, Wang K, Li Y, Wang Y and Du J: ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response. Oncol Rep. 37:761–767. 2017. View Article : Google Scholar : PubMed/NCBI
24	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
25	Zhao X and Chu J: MicroRNA-379 suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma by targeting tumor protein D52. Exp Ther Med. 16:1232–1240. 2018.PubMed/NCBI
26	Ma Z, Yu YR, Badea CT, Kovacs JJ, Xiong X, Comhair S, Piantadosi CA and Rajagopal S: Vascular endothelial growth factor receptor 3 regulates endothelial function through β-arrestin. Circulation. 139:1629–1642. 2019. View Article : Google Scholar : PubMed/NCBI
27	Zecchini V, Madhu B, Russell R, Gomes NP, Warren A, Gaude E, Borlido J, Stark R, Zecchini HI, Rao R, et al: Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer. EMBO J. 33:1365–1382. 2014. View Article : Google Scholar : PubMed/NCBI
28	Son D, Kim Y, Lim S, Kang HG, Kim DH, Park JW, Cheong W, Kong HK, Han W, Park WY, et al: MiR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer. Cancer Lett. 454:224–233. 2019. View Article : Google Scholar : PubMed/NCBI
29	Zhang Z, Zhong X, Xiao Y and Chen C: MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation. Oncol Rep. 41:619–629. 2019.PubMed/NCBI
30	Zhan Y, Xu C, Liu Z, Yang Y, Tan S, Yang Y, Jiang J, Liu H, Chen J and Wu B: β-Arrestin1 inhibits chemotherapy-induced intestinal stem cell apoptosis and mucositis. Cell Death Dis. 7:e22292016. View Article : Google Scholar : PubMed/NCBI