MicroRNA‑891a‑5p is a novel biomarker for non‑small cell lung cancer and targets HOXA5 to regulate tumor cell biological function

Wan,Nianqing; Zheng,Jianxiao

doi:10.3892/ol.2021.12768

MicroRNA‑891a‑5p is a novel biomarker for non‑small cell lung cancer and targets HOXA5 to regulate tumor cell biological function

Authors:
- Nianqing Wan
- Jianxiao Zheng
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Affiliations: Department of Integrated Traditional Chinese and Western Medicine, Yueqing People's Hospital, Yueqing, Zhejiang 325600, P.R. China
Published online on: May 2, 2021 https://doi.org/10.3892/ol.2021.12768
Article Number: 507
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous studies have shown that the dysregulation of microRNA (miRNA/miR) is an important factor in the pathogenesis of lung cancer. However, the role of miR‑891a‑5p in non‑small cell lung cancer (NSCLC) remains unclear. Therefore, the present study aimed to examine the clinical value and biological function of miR‑891a‑5p in NSCLC. The mRNA expression level of miR‑891a‑5p in NSCLC was determined using reverse transcription‑quantitative PCR and was used to determine the diagnostic value of miR‑891a‑5p, by creating a receiver operating characteristic curve. Kaplan‑Meier and Cox regression analyses were used to evaluate its prognostic value in patients with NSCLC. Furthermore, cell experiments were performed to investigate the underlying mechanisms and functional role of miR‑891a‑5p in NSCLC progression. The results indicated that miR‑891a‑5p expression level was significantly higher in serum and tissues from patients with NSCLC and NSCLC cell lines. In addition, serum miR‑891a‑5p was found to have a diagnostic value in patients with NSCLC, and the increase in the expression level of miR‑891a‑5p in tumor tissues was associated with differentiation, and the tumor, node and metastases stages of cancer, which could be used for NSCLC prognosis. In addition, the experiments revealed that NSCLC cell proliferation, invasion and migration were significantly increased by the overexpression of miR‑891a‑5p and were significantly reduced by its downregulation. Furthermore, a luciferase reporter assay and the protein expression levels of HOXA5 showed that HOXA5 might be a miR‑891a‑5p target gene. In summary, the results indicated that high miR‑891a‑5p expression level could be a novel biomarker in patients with NSCLC and that it promoted tumor cell proliferation, invasion and migration. HOXA5 may be a target of miR‑891a‑5p, which may mediate miR‑891a‑5p function in NSCLC.

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1	Nasim F, Sabath BF and Eapen GA: Lung Cancer. Med Clin North Am. 103:463–473. 2019. View Article : Google Scholar : PubMed/NCBI
2	Võsa U, Vooder T, Kolde R, Vilo J, Metspalu A and Annilo T: Meta-analysis of microRNA expression in lung cancer. Int J Cancer. 132:2884–2893. 2013. View Article : Google Scholar
3	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
4	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
5	Liu J, Bian T, Feng J, Qian L, Zhang J, Jiang D, Zhang Q, Li X, Liu Y and Shi J: miR-335 inhibited cell proliferation of lung cancer cells by target Tra2β. Cancer Sci. 109:289–296. 2018. View Article : Google Scholar : PubMed/NCBI
6	Wu YL, Sun Y, Zhou CC, Zhang L, Yu SY, Ma SL, Han LL, Zhang XQ and Orlando M: Survival without common toxicity criteria grade 3/4 toxicity following second-line treatment with pemetrexed for nonsquamous non-small cell lung cancer in Chinese patients. Chin Med J (Engl). 126:4624–4628. 2013.PubMed/NCBI
7	Woodard GA, Jones KD and Jablons DM: Lung Cancer Staging and Prognosis. Cancer Treat Res. 170:47–75. 2016. View Article : Google Scholar : PubMed/NCBI
8	Turchinovich A, Weiz L and Burwinkel B: Extracellular miRNAs: The mystery of their origin and function. Trends Biochem Sci. 37:460–465. 2012. View Article : Google Scholar : PubMed/NCBI
9	Barbato S, Solaini G and Fabbri M: MicroRNAs in oncogenesis and tumor suppression. Int Rev Cell Mol Biol. 333:229–268. 2017. View Article : Google Scholar : PubMed/NCBI
10	Zhang X, Xu X, Ge G, Zang X, Shao M, Zou S, Zhang Y, Mao Z, Zhang J, Mao F, et al: miR 498 inhibits the growth and metastasis of liver cancer by targeting ZEB2. Oncol Rep. 41:1638–1648. 2019.PubMed/NCBI
11	Yuan J, Su Z, Gu W, Shen X, Zhao Q, Shi L, Jin C, Wang X, Cong H and Ju S: MiR-19b and miR-20a suppress apoptosis, promote proliferation and induce tumorigenicity of multiple myeloma cells by targeting PTEN. Cancer Biomark. 24:279–289. 2019. View Article : Google Scholar : PubMed/NCBI
12	Ganju A, Khan S, Hafeez BB, Behrman SW, Yallapu MM, Chauhan SC and Jaggi M: miRNA nanotherapeutics for cancer. Drug Discov Today. 22:424–432. 2017. View Article : Google Scholar : PubMed/NCBI
13	Lin K, Xu T, He BS, Pan YQ, Sun HL, Peng HX, Hu XX and Wang SK: MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma. OncoTargets Ther. 9:5679–5692. 2016. View Article : Google Scholar : PubMed/NCBI
14	Lee HY, Han SS, Rhee H, Park JH, Lee JS, Oh YM, Choi SS, Shin SH and Kim WJ: Differential expression of microRNAs and their target genes in non-small-cell lung cancer. Mol Med Rep. 11:2034–2040. 2015. View Article : Google Scholar : PubMed/NCBI
15	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
16	Lin Z, Zhao J, Wang X, Zhu X and Gong L: Overexpression of microRNA-497 suppresses cell proliferation and induces apoptosis through targeting paired box 2 in human ovarian cancer. Oncol Rep. 36:2101–2107. 2016. View Article : Google Scholar : PubMed/NCBI
17	Chen Z, Fillmore CM, Hammerman PS, Kim CF and Wong KK: Non-small-cell lung cancers: A heterogeneous set of diseases. Nat Rev Cancer. 14:535–546. 2014. View Article : Google Scholar : PubMed/NCBI
18	Akhurst T: Staging of non-small-cell lung cancer. PET Clin. 13:1–10. 2018. View Article : Google Scholar : PubMed/NCBI
19	Gao L, Yan SB, Yang J, Kong JL, Shi K, Ma FC, Huang LZ, Luo J, Yin SY, He RQ, et al: MiR-182-5p and its target HOXA9 in non-small cell lung cancer: A clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip. BMC Med Genomics. 13:32020. View Article : Google Scholar : PubMed/NCBI
20	Chen Y, Min L, Ren C, Xu X, Yang J, Sun X, Wang T, Wang F, Sun C and Zhang X: miRNA-148a serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer. PLoS One. 12:e01717512017. View Article : Google Scholar : PubMed/NCBI
21	Tan T, Xu XH, Lu XH and Wang XW: MiRNA-200a-3p suppresses the proliferation, migration and invasion of non-small cell lung cancer through targeting IRS2. Eur Rev Med Pharmacol Sci. 24:712–720. 2020.PubMed/NCBI
22	Zhang L, Deng T, Li X, Liu H, Zhou H, Ma J, Wu M, Zhou M, Shen S, Li X, et al: microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network. Carcinogenesis. 31:559–566. 2010. View Article : Google Scholar : PubMed/NCBI
23	Cai H, Lin H, Cao W, Sun J, Huang Y and Fang Y: The downregulation of miR-519a predicts poor prognosis and contributes to tumor progression in gastric cancer. Int J Clin Exp Pathol. 12:2496–2505. 2019.PubMed/NCBI
24	Shi X and Guan X: MicroRNA-99b predicts clinical outcome of osteosarcoma and suppresses tumor cell proliferation, migration and invasion. Diagn Pathol. 14:1172019. View Article : Google Scholar : PubMed/NCBI
25	Liang H, Huang W, Wang Y, Ding L and Zeng L: Overexpression of MiR-146a-5p Upregulates lncRNA HOTAIR in triple-negative breast cancer cells and predicts poor prognosis. Technol Cancer Res Treat. 18:15330338198829492019. View Article : Google Scholar : PubMed/NCBI
26	Gu GM, Zhan YY, Abuduwaili K, Wang XL, Li XQ, Zhu HG and Liu CL: MiR-940 inhibits the progression of NSCLC by targeting FAM83F. Eur Rev Med Pharmacol Sci. 22:5964–5971. 2018.PubMed/NCBI
27	Feng QQ, Dong ZQ, Zhou Y, Zhang H and Long C: miR-16-1-3p targets TWIST1 to inhibit cell proliferation and invasion in NSCLC. Bratisl Lek Listy. 119:60–65. 2018.PubMed/NCBI
28	Yao S, Hu M, Hao T, Li W, Xue X, Xue M, Zhu X, Zhou F, Qin D, Yan Q, et al: MiRNA-891a-5p mediates HIV-1 Tat and KSHV Orf-K1 synergistic induction of angiogenesis by activating NF-κB signaling. Nucleic Acids Res. 47:27002019. View Article : Google Scholar : PubMed/NCBI
29	Zhang Z, Xu L, He L, Wang J, Shi X, Li Z, Shi S, Hou K, Teng Y and Qu X: MiR-891a-5p as a prognostic marker and therapeutic target for hormone receptor-positive breast cancer. J Cancer. 11:3771–3782. 2020. View Article : Google Scholar : PubMed/NCBI
30	Lu X and Lu J: The significance of detection of serum miR-423-5p and miR-484 for diagnosis of colorectal cancer. Clin Lab. 61:187–190. 2015. View Article : Google Scholar : PubMed/NCBI
31	Kamarudin AN, Cox T and Kolamunnage-Dona R: Time-dependent ROC curve analysis in medical research: Current methods and applications. BMC Med Res Methodol. 17:532017. View Article : Google Scholar : PubMed/NCBI
32	Enane FO, Saunthararajah Y and Korc M: Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells. Cell Death Dis. 9:9122018. View Article : Google Scholar : PubMed/NCBI
33	Cao W, Xu Y, Luo D, Saeed M and Sun C: Hoxa5 promotes adipose differentiation via increasing DNA methylation level and inhibiting PKA/HSL signal pathway in Mice. Cell Physiol Biochem. 45:1023–1033. 2018. View Article : Google Scholar : PubMed/NCBI
34	Li D, Bai Y, Feng Z, Li W, Yang C, Guo Y, Lin C, Zhang Y, He Q, Hu G, et al: Study of promoter methylation patterns of HOXA2, HOXA5, and HOXA6 and its clinicopathological characteristics in colorectal cancer. Front Oncol. 9:3942019. View Article : Google Scholar : PubMed/NCBI
35	Wu Y, Zhou T, Tang Q and Xiao J: HOXA5 inhibits tumor growth of gastric cancer under the regulation of microRNA-196a. Gene. 681:62–68. 2019. View Article : Google Scholar : PubMed/NCBI
36	Ordóñez-Morán P, Dafflon C, Imajo M, Nishida E and Huelsken J: HOXA5 counteracts stem cell traits by inhibiting Wnt signaling in colorectal cancer. Cancer Cell. 28:815–829. 2015. View Article : Google Scholar
37	Liu XH, Lu KH, Wang KM, Sun M, Zhang EB, Yang JS, Yin DD, Liu ZL, Zhou J, Liu ZJ, et al: MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5. BMC Cancer. 12:3482012. View Article : Google Scholar : PubMed/NCBI
38	Chang CJ, Chen YL, Hsieh CH, Liu YJ, Yu SL, Chen JJ and Wang CC: HOXA5 and p53 cooperate to suppress lung cancer cell invasion and serve as good prognostic factors in non-small cell lung cancer. J Cancer. 8:1071–1081. 2017. View Article : Google Scholar : PubMed/NCBI