miR‑1271‑5p inhibits cell proliferation and induces apoptosis in acute myeloid leukemia by targeting ZIC2

Chen,Xiaohe; Yang,Shouhang; Zeng,Jue; Chen,Ming

doi:10.3892/mmr.2018.9680

miR‑1271‑5p inhibits cell proliferation and induces apoptosis in acute myeloid leukemia by targeting ZIC2

Authors:
- Xiaohe Chen
- Shouhang Yang
- Jue Zeng
- Ming Chen
View Affiliations

Affiliations: Department of Blood Transfusion, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang 325200, P.R. China
Published online on: November 21, 2018 https://doi.org/10.3892/mmr.2018.9680
Pages: 508-514
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs) have been demonstrated to regulate the progression of numerous types of cancer, including acute myeloid leukemia (AML). Previous studies demonstrated that miR‑1271‑5p functions as a tumor suppressor; however, the roles of miR‑1271‑5p in AML remain unknown. In the present study, miR‑1271‑5p was significantly downregulated in AML tissues compared with normal tissues by reverse transcription‑quantitative polymerase chain reaction analysis. Furthermore, the expression levels of miR‑1271‑5p in patients with AML may function as a prognostic marker. In addition, overexpression of miR‑1271‑5p significantly suppressed the proliferation and induced apoptosis of AML cells by Cell Counting kit‑8 and fluorescence activated cell sorter assays; miR‑1271‑5p downregulation exhibited opposing effects. Additionally, transcription factor ZIC2 may be a direct target of miR‑1271‑5p in AML cells, which was demonstrated by a luciferase reporter assay and RNA pulldown assay. Overexpression of miR‑1271‑5p significantly reduced the mRNA and protein expression levels of ZIC2 in AML193 and OCI‑AML2 cells by reverse transcription‑quantitative polymerase chain reaction analysis and western blotting. Furthermore, an inverse correlation between miR‑1271‑5p and ZIC2 expression in AML samples was observed. In summary, ZIC2 was upregulated in AML tissues, and restoration of ZIC2 expression was able to promote the proliferation and reduce the apoptosis of AML cells transfected with miR‑1271‑5p mimics. The results of the present study demonstrated that miR‑1271‑5p inhibited the progression of AML by targeting ZIC2.

View Figures

View References

1	Estey EH: Acute myeloid leukemia: 2013 update on risk-stratification and management. Am J Hematol. 88:318–327. 2013. View Article : Google Scholar : PubMed/NCBI
2	Dombret H and Gardin C: An update of current treatments for adult acute myeloid leukemia. Blood. 127:53–61. 2016. View Article : Google Scholar : PubMed/NCBI
3	Khalaj M, Tavakkoli M, Stranahan AW and Park CY: Pathogenic microRNA's in myeloid malignancies. Front Genet. 5:3612014. View Article : Google Scholar : PubMed/NCBI
4	Marcucci G, Haferlach T and Döhner H: Molecular genetics of adult acute myeloid leukemia: Prognostic and therapeutic implications. J Clin Oncol. 29:475–486. 2011. View Article : Google Scholar : PubMed/NCBI
5	Estey E and Döhner H: Acute myeloid leukaemia. Lancet. 368:1894–1907. 2006. View Article : Google Scholar : PubMed/NCBI
6	Baldus CD, Mrózek K, Marcucci G and Bloomfield CD: Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: A concise review. Br J Haematol. 137:387–400. 2007. View Article : Google Scholar : PubMed/NCBI
7	Bi L, Zhou B, Li H, He L, Wang C, Wang Z, Zhu L, Chen M and Gao S: A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia. BMC Cancer. 18:1822018. View Article : Google Scholar : PubMed/NCBI
8	Zhang TJ, Lin J, Zhou JD, Li XX, Zhang W, Guo H, Xu ZJ, Yan Y, Ma JC and Qian J: High bone marrow miR-19b level predicts poor prognosis and disease recurrence in de novo acute myeloid leukemia. Gene. 640:79–85. 2018. View Article : Google Scholar : PubMed/NCBI
9	Zhang S, Zhang Q, Shi G and Yin J: MiR-182-5p regulates BCL2L12 and BCL2 expression in acute myeloid leukemia as a potential therapeutic target. Biomed Pharmacother. 97:1189–1194. 2018. View Article : Google Scholar : PubMed/NCBI
10	Zebisch A, Hatzl S, Pichler M, Wölfler A and Sill H: Therapeutic resistance in acute myeloid leukemia: The role of non-coding RNAs. Int J Mol Sci. 17(pii): E20802016. View Article : Google Scholar : PubMed/NCBI
11	Fan N, Zhang J, Cheng C, Zhang X, Feng J and Kong R: MicroRNA-384 represses the growth and invasion of non-small-cell lung cancer by targeting astrocyte elevated gene-1/Wnt signaling. Biomed Pharmacother. 95:1331–1337. 2017. View Article : Google Scholar : PubMed/NCBI
12	Wang Y, Xue J, Kuang H, Zhou X, Liao L and Yin F: microRNA-1297 inhibits the growth and metastasis of colorectal cancer by suppressing cyclin D2 expression. DNA Cell Biol. 36:991–999. 2017. View Article : Google Scholar : PubMed/NCBI
13	You Y, Tan J, Gong Y, Dai H, Chen H, Xu X, Yang A, Zhang Y and Bie P: MicroRNA-216b-5p Functions as a Tumor-suppressive RNA by targeting TPT1 in pancreatic cancer cells. J Cancer. 8:2854–2865. 2017. View Article : Google Scholar : PubMed/NCBI
14	Ma QL, Wang JH, Yang M, Wang HP and Jin J: MiR-362-5p as a novel prognostic predictor of cytogenetically normal acute myeloid leukemia. J Transl Med. 16:682018. View Article : Google Scholar : PubMed/NCBI
15	Huang Y, Zou Y, Lin L, Ma X and Chen H: Identification of serum miR-34a as a potential biomarker in acute myeloid leukemia. Cancer Biomark. 22:799–805. 2018. View Article : Google Scholar : PubMed/NCBI
16	Ding C, Chen SN, Macleod RAF, Drexler HG, Nagel S, Wu DP, Sun AN and Dai HP: MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death. Ups J Med Sci. 123:19–27. 2018. View Article : Google Scholar : PubMed/NCBI
17	Zhao Q, Li J, Chen S, Shen K, Ai G, Dai X, Xie B, Shi Y, Jiang S, Feng J and Li W: Decreased miR-144 expression as a non-invasive biomarker for acute myeloid leukemia patients. Pharmazie. 72:232–235. 2017.PubMed/NCBI
18	Wu Z, Hu Z, Han X, Li Z, Zhu Q, Wang Y, Zheng Q and Yan J: The BET-Bromodomain Inhibitor JQ1 synergized ABT-263 against colorectal cancer cells through suppressing c-Myc-induced miR-1271-5p expression. Biomed Pharmacother. 95:1574–1579. 2017. View Article : Google Scholar : PubMed/NCBI
19	Lin MF, Yang YF, Peng ZP, Zhang MF, Liang JY, Chen W, Liu XH and Zheng YL: FOXK2, regulted by miR-1271-5p, promotes cell growth and indicates unfavorable prognosis in hepatocellular carcinoma. Int J Biochem Cell Biol. 88:155–161. 2017. View Article : Google Scholar : PubMed/NCBI
20	Chen Y, Li J, Hu J, Zheng J, Zheng Z, Liu T, Lin Z and Lin M: Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells. Int J Oncol. 45:2076–2084. 2014. View Article : Google Scholar : PubMed/NCBI
21	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
22	Liao Q, Wang B, Li X and Jiang G: miRNAs in acute myeloid leukemia. Oncotarget. 8:3666–3682. 2017. View Article : Google Scholar : PubMed/NCBI
23	Tian C, Zheng G, Zhuang H, Li X, Hu D, Zhu L, Wang T, You MJ and Zhang Y: MicroRNA-494 activation suppresses bone marrow stromal cell-mediated drug resistance in acute myeloid leukemia cells. J Cell Physiol. 232:1387–1395. 2017. View Article : Google Scholar : PubMed/NCBI
24	Yang DQ, Zhou JD, Wang YX, Deng ZQ, Yang J, Yao DM, Qian Z, Yang L, Lin J and Qian J: Low miR-34c expression is associated with poor outcome in de novo acute myeloid leukemia. Int J Lab Hematol. 39:42–50. 2017. View Article : Google Scholar : PubMed/NCBI
25	Jiang X, Hu C, Arnovitz S, Bugno J, Yu M, Zuo Z, Chen P, Huang H, Ulrich B, Gurbuxani S, et al: miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia. Nat Commun. 7:114522016. View Article : Google Scholar : PubMed/NCBI
26	Inaguma S, Ito H, Riku M, Ikeda H and Kasai K: Addiction of pancreatic cancer cells to zinc-finger transcription factor ZIC2. Oncotarget. 6:28257–28268. 2015. View Article : Google Scholar : PubMed/NCBI
27	Lu SX, Zhang CZ, Luo RZ, Wang CH, Liu LL, Fu J, Zhang L, Wang H, Xie D and Yun JP: Zic2 promotes tumor growth and metastasis via PAK4 in hepatocellular carcinoma. Cancer Lett. 402:71–80. 2017. View Article : Google Scholar : PubMed/NCBI
28	Marchini S, Poynor E, Barakat RR, Clivio L, Cinquini M, Fruscio R, Porcu L, Bussani C, D'Incalci M, Erba E, et al: The zinc finger gene ZIC2 has features of an oncogene and its overexpression correlates strongly with the clinical course of epithelial ovarian cancer. Clin Cancer Res. 18:4313–4324. 2012. View Article : Google Scholar : PubMed/NCBI
29	Sakuma K, Kasamatsu A, Yamatoji M, Yamano Y, Fushimi K, Iyoda M, Ogoshi K, Shinozuka K, Ogawara K, Shiiba M, et al: Expression status of Zic family member 2 as a prognostic marker for oral squamous cell carcinoma. J Cancer Res Clin Oncol. 136:553–559. 2010. View Article : Google Scholar : PubMed/NCBI
30	Chan DW, Liu VW, Leung LY, Yao KM, Chan KK, Cheung AN and Ngan HY: Zic2 synergistically enhances Hedgehog signalling through nuclear retention of Gli1 in cervical cancer cells. J Pathol. 225:525–534. 2011. View Article : Google Scholar : PubMed/NCBI
31	Shen ZH, Zhao KM and Du T: HOXA10 promotes nasopharyngeal carcinoma cell proliferation and invasion via inducing the expression of ZIC2. Eur Rev Med Pharmacol Sci. 21:945–952. 2017.PubMed/NCBI
32	Zhu P, Wang Y, He L, Huang G, Du Y, Zhang G, Yan X, Xia P, Ye B, Wang S, et al: ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells. J Clin Invest. 125:3795–3808. 2015. View Article : Google Scholar : PubMed/NCBI
33	Wang J, Ma W and Liu Y: Long non-coding RNA HULC promotes bladder cancer cells proliferation but inhibits apoptosis via regulation of ZIC2 and PI3K/AKT signaling pathway. Cancer Biomark. 20:425–434. 2017. View Article : Google Scholar : PubMed/NCBI