miR‑101‑3p sensitizes lung adenocarcinoma cells to irradiation via targeting BIRC5

Meng,Xin; Sun,Yanfei; Liu,Shiying; Mu,Yanchao

doi:10.3892/ol.2021.12543

miR‑101‑3p sensitizes lung adenocarcinoma cells to irradiation via targeting BIRC5

Authors:
- Xin Meng
- Yanfei Sun
- Shiying Liu
- Yanchao Mu
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Affiliations: Department of Hyperbaric Oxygen, The First Affiliated Hospital of China Medical University, Liaoning, Shenyang 110001, P.R. China, Trauma Center/Burn Ward, The First Affiliated Hospital of China Medical University, Liaoning, Shenyang 110001, P.R. China, School of Nursing, China Medical University, Liaoning, Shenyang 110001, P.R. China, Department of Laboratory Medicine, Anyang Maternity and Child Healthcare Hospital, Anyang, Henan 455000, P.R. China
Published online on: February 10, 2021 https://doi.org/10.3892/ol.2021.12543
Article Number: 282
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung adenocarcinoma (LUAD) has been considered as the most common cause of cancer‑associated mortality. Radiotherapy resistance is one of the main reasons for LUAD treatment failure. The microRNA (miR)‑101‑3p has been previously reported to function as a tumor suppressor in several types of cancer, including LUAD. The present study aimed to explore the role and mechanism of miR‑101‑3p on radioresistance of lung adenocarcinoma cells through bioinformatics analysis and biological experiments. Based on the analysis of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data, it was demonstrated that the expression of miR‑101‑3p was low in LUAD tissues compared with normal lung tissues and was associated with poor prognosis of patients with LUAD. The results of the CCK‑8 assay, colony formation assay, immunofluorescence staining, caspase‑3 activity assay and western blotting demonstrated that miR‑101‑3p overexpression sensitized LUAD cells to ionizing radiation by decreasing the abilities of LUAD cell proliferation, colony formation, DNA damage repair and increasing caspase‑3 activity and apoptosis of LUAD cells following ionizing radiation. Furthermore, according to bioinformatics analysis and luciferase assay, baculoviral IAP repeat containing 5 (BIRC5) was identified as a direct target of miR‑101‑3p. Increased BIRC5 expression reversed the miR‑101‑3p‑mediated increase in LUAD cell radiotherapy sensitivity. Taken together, the results of the present study demonstrated that miR‑101‑3p may be considered as a potential target that can enhance LUAD cell sensitivity to radiotherapy, which may provide a new strategy to improve therapy in patients with LUAD.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Chen J, Xu Y, Tao L, Pan Y, Zhang K, Wang R, Chen LB and Chu X: miRNA-26a contributes to the acquisition of malignant behaviors of doctaxel-resistant lung adenocarcinoma cells through targeting EZH2. Cell Physiol Biochem. 41:583–597. 2017. 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	Jonas S and Izaurralde E: Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 16:421–433. 2015. View Article : Google Scholar : PubMed/NCBI
5	Rupaimoole R and Slack FJ: MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 16:203–222. 2017. View Article : Google Scholar : PubMed/NCBI
6	Di Leva G, Garofalo M and Croce CM: MicroRNAs in cancer. Annu Rev Pathol. 9:287–314. 2014. View Article : Google Scholar : PubMed/NCBI
7	Huang T, Yin L, Wu J, Gu JJ, Wu JZ, Chen D, Yu HL, Ding K, Zhang N, Du MY, et al: MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis. J Exp Clin Cancer Res. 35:1882016. View Article : Google Scholar : PubMed/NCBI
8	Chen W, Song J, Bian H, Yang X, Xie X, Zhu Q, Qin C and Qi J: The functions and targets of miR-212 as a potential biomarker of cancer diagnosis and therapy. J Cell Mol Med. 24:2392–2401. 2020. View Article : Google Scholar : PubMed/NCBI
9	Wu X, Zhou J, Wu Z, Chen C, Liu J, Wu G, Zhai J, Liu F and Li G: miR-101-3p suppresses HOX transcript antisense RNA (HOTAIR)-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells. Oncol Res. 25:1383–1390. 2017. View Article : Google Scholar : PubMed/NCBI
10	Hou Y, Li L, Ju Y, Lu Y, Chang L and Xiang X: miR-101-3p regulates the viability of lung squamous carcinoma cells via targeting EZH2. J Cell Biochem. 118:3142–3149. 2017. View Article : Google Scholar : PubMed/NCBI
11	Li B, Xie D and Zhang H: MicroRNA-101-3p advances cisplatin sensitivity in bladder urothelial carcinoma through targeted silencing EZH2. J Cancer. 10:2628–2634. 2019. View Article : Google Scholar : PubMed/NCBI
12	Yamamoto H, Ngan CY and Monden M: Cancer cells survive with survivin. Cancer Sci. 99:1709–1714. 2008. View Article : Google Scholar : PubMed/NCBI
13	Pennati M, Folini M and Zaffaroni N: Targeting survivin in cancer therapy. Expert Opin Ther Targets. 12:463–476. 2008. View Article : Google Scholar : PubMed/NCBI
14	Greve B, Sheikh-Mounessi F, Kemper B, Ernst I, Götte M and Eich HT: Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma. Strahlenther Onkol. 188:1038–1047. 2012. View Article : Google Scholar : PubMed/NCBI
15	Reichert S, Rödel C, Mirsch J, Harter PN, Tomicic MT, Mittelbronn M, Kaina B and Rödel F: Survivin inhibition and DNA double-strand break repair: A molecular mechanism to overcome radioresistance in glioblastoma. Radiother Oncol. 101:51–58. 2011. View Article : Google Scholar : PubMed/NCBI
16	Erpolat OP, Gocun PU, Akmansu M, Karakus E and Akyol G: High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer. Strahlenther Onkol. 188:248–254. 2012. View Article : Google Scholar : PubMed/NCBI
17	Romagnoli M, Séveno C, Bataille R and Barillé-Nion S: Survivin in cancerology: Molecular aspects and therapeutic applications. Med Sci (Paris). 24:821–827. 2008.(In French). View Article : Google Scholar : PubMed/NCBI
18	Sprenger T, Rödel F, Beissbarth T, Conradi LC, Rothe H, Homayounfar K, Wolff HA, Ghadimi BM, Yildirim M, Becker H, et al: Failure of downregulation of survivin following neoadjuvant radiochemotherapy in rectal cancer is associated with distant metastases and shortened survival. Clin Cancer Res. 17:1623–1631. 2011. View Article : Google Scholar : PubMed/NCBI
19	Bjaanaes MM, Halvorsen AR, Solberg S, Jørgensen L, Dragani TA, Galvan A, Colombo F, Anderlini M, Pastorino U, Kure E, et al: Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas. Int J Cancer. 135:1812–1821. 2014. View Article : Google Scholar : PubMed/NCBI
20	Wu KH, Zhou B, Lu SH, Feng B, Yang SG, Du WT, Gu DS, Han ZC and Liu YL: In vitro and in vivo differentiation of human umbilical cord derived stem cells into endothelial cells. J Cell Biochem. 100:608–616. 2007. View Article : Google Scholar : PubMed/NCBI
21	Yang JH, Li JH, Shao P, Zhou H, Chen YQ and Qu LH: StarBase: A database for exploring microRNA-mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data. Nucleic Acids Res. 39((Database Issue)): D202–D209. 2011. View Article : Google Scholar : PubMed/NCBI
22	Menyhárt O, Nagy Á and Győrffy B: Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma. R Soc Open Sci. 5:1810062018. 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(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Mariotti LG, Pirovano G, Savage KI, Ghita M, Ottolenghi A, Prise KM and Schettino G: Use of the γ-H2AX assay to investigate DNA repair dynamics following multiple radiation exposures. PLoS One. 8:e795412013. View Article : Google Scholar : PubMed/NCBI
25	Zhang J, Shen L and Sun LQ: The regulation of radiosensitivity by p53 and its acetylation. Cancer Lett. 363:108–118. 2015. View Article : Google Scholar : PubMed/NCBI
26	Véquaud E, Desplanques G, Jézéquel P, Juin P and Barillé-Nion S: Survivin contributes to DNA repair by homologous recombination in breast cancer cells. Breast Cancer Res. Treat. 155:53–63. 2016.
27	Dong Y, Zhang D, Cai M, Luo Z, Zhu Y, Gong L, Lei Y, Tan X, Zhu Q and Han S: SPOP regulates the DNA damage response and lung adenocarcinoma cell response to radiation. Am J Cancer Res. 9:1469–1483. 2019.PubMed/NCBI
28	Yang S, Chen J, Guo Y, Lin H, Zhang Z, Feng G, Hao Y, Cheng J, Liang P, Chen K, et al: Identification of prognostic biomarkers for response to radiotherapy by DNA microarray in nasopharyngeal carcinoma patients. Int J Oncol. 40:1590–1600. 2012.PubMed/NCBI
29	Salim H, Akbar NS, Zong D, Vaculova AH, Lewensohn R, Moshfegh A, Viktorsson K and Zhivotovsky B: miRNA-214 modulates radiotherapy response of non-small cell lung cancer cells through regulation of p38MAPK, apoptosis and senescence. Br J Cancer. 107:1361–1373. 2012. View Article : Google Scholar : PubMed/NCBI
30	Fang H, Xie J, Zhang M, Zhao Z, Wan Y and Yao Y: miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN. Am J Transl Res. 9:953–961. 2017.PubMed/NCBI
31	Thu KL, Chari R, Lockwood WW, Lam S and Lam WL: miR-101 DNA copy loss is a prominent subtype specific event in lung cancer. J Thorac Oncol. 6:1594–1598. 2011. View Article : Google Scholar : PubMed/NCBI
32	Li L, Shao MY, Zou SC, Xiao ZF and Chen ZC: miR-101-3p inhibits EMT to attenuate proliferation and metastasis in glioblastoma by targeting TRIM44. J Neurooncol. 141:19–30. 2019. View Article : Google Scholar : PubMed/NCBI
33	Bao J, Xu Y, Wang Q, Zhang J, Li Z, Li D and Li J: miR-101 alleviates chemoresistance of gastric cancer cells by targeting ANXA2. Biomed Pharmacother. 92:1030–1037. 2017. View Article : Google Scholar : PubMed/NCBI
34	Chen LG, Xia YJ and Cui Y: Upregulation of miR-101 enhances the cytotoxic effect of anticancer drugs through inhibition of colon cancer cell proliferation. Oncol Rep. 38:100–108. 2017. View Article : Google Scholar : PubMed/NCBI
35	Xu F, Liao JZ, Xiang GY, Zhao PX, Ye F, Zhao Q and He XX: miR-101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma. Cancer Med. 6:651–661. 2017. View Article : Google Scholar : PubMed/NCBI
36	Altieri DC: Molecular circuits of apoptosis regulation and cell division control: The survivin paradigm. J Cell Biochem. 92:656–663. 2004. View Article : Google Scholar : PubMed/NCBI
37	Altieri DC: Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 8:61–70. 2008. View Article : Google Scholar : PubMed/NCBI
38	Hu S, Qu Y, Xu X, Xu Q, Geng J and Xu J: Nuclear survivin and its relationship to DNA damage repair genes in non-small cell lung cancer investigated using tissue array. PLoS One. 8:e741612013. View Article : Google Scholar : PubMed/NCBI