MicroRNA‑874 inhibits proliferation and invasion of pancreatic ductal adenocarcinoma cells by directly targeting paired box 6 Retraction in /10.3892/mmr.2022.12873

Diao,Jiandong; Su,Xiaoyun; Cao,Ling; Yang,Yongjing; Liu,Yanling

doi:10.3892/mmr.2018.9069

MicroRNA‑874 inhibits proliferation and invasion of pancreatic ductal adenocarcinoma cells by directly targeting paired box 6

Retraction in: /10.3892/mmr.2022.12873

Authors:
- Jiandong Diao
- Xiaoyun Su
- Ling Cao
- Yongjing Yang
- Yanling Liu
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Affiliations: Department of Oncology and Hematology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130012, P.R. China, Department of Radiation Oncology, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China, Department of Oncology, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/mmr.2018.9069
Pages: 1188-1196

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Abstract

Studies have demonstrated that a number of microRNAs (miRNAs) are dysregulated in pancreatic ductal adenocarcinoma (PDAC), and alterations in their expression may affect the onset and progression of PDAC. Therefore, the expression patterns, biological functions and associated molecular mechanisms of miRNAs in PDAC should be elucidated for the development of novel therapeutic methods. Previous studies reported significant miRNA‑874 (miR‑874) dysregulation in multiple types of human cancer. However, the expression pattern, possible roles and underlying mechanisms of miR‑874 in PDAC remain to be elucidated. This study evaluated miR‑874 expression in PDAC and examined its biological functions and underlying mechanism of action in PDAC progression. miR‑874 expression was downregulated in PDAC tissues and cell lines. Functional experiments demonstrated that upregulation of miR‑874 inhibited cell proliferation and invasion in PDAC. Additionally, paired box 6 (PAX6) was predicted as a putative target of miR‑874 using bioinformatics analysis. Further experiments demonstrated that PAX6 may be the direct target gene of miR‑874 in PDAC. PAX6 knockdown exhibited similar inhibitory effects to miR‑874 overexpression in PDAC cells. In addition, restored PAX6 expression may reverse the suppressive roles of miR‑874 overexpression in PDAC cells. The results demonstrated that miR‑874 may serve tumor suppressive roles in PDAC by directly targeting PAX6. Therefore, miR‑874 may exhibit potential applications for treatment of patients with PDAC.

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1	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
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
3	Moir J, White SA, French JJ, Littler P and Manas DM: Systematic review of irreversible electroporation in the treatment of advanced pancreatic cancer. Eur J Surg Oncol. 40:1598–1604. 2014. View Article : Google Scholar : PubMed/NCBI
4	Burkey MD, Feirman S, Wang H, Choudhury SR, Grover S and Johnston FM: The association between smokeless tobacco use and pancreatic adenocarcinoma: A systematic review. Cancer Epidemiol. 38:647–653. 2014. View Article : Google Scholar : PubMed/NCBI
5	Li H, Wu Y and Li P: MicroRNA-452 suppresses pancreatic cancer migration and invasion by directly targeting B-cell-specific Moloney murine leukemia virus insertion site 1. Oncol Lett. 14:3235–3242. 2017. View Article : Google Scholar : PubMed/NCBI
6	Modolell I, Guarner L and Malagelada JR: Vagaries of clinical presentation of pancreatic and biliary tract cancer. Ann Oncol. 10 Suppl 4:S82–S84. 1999. View Article : Google Scholar
7	Ryan DP, Hong TS and Bardeesy N: Pancreatic adenocarcinoma. N Engl J Med. 371:1039–1049. 2014. View Article : Google Scholar : PubMed/NCBI
8	Arslan C and Yalcin S: Current and future systemic treatment options in metastatic pancreatic cancer. J Gastrointest Oncol. 5:280–295. 2014.PubMed/NCBI
9	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
10	Lytle JR, Yario TA and Steitz JA: Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci USA. 104:9667–9672. 2007. View Article : Google Scholar : PubMed/NCBI
11	Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M and Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
12	Lin S and Gregory RI: MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 15:321–333. 2015. View Article : Google Scholar : PubMed/NCBI
13	Davis-Dusenbery BN and Hata A: MicroRNA in cancer: The Involvement of Aberrant MicroRNA biogenesis regulatory pathways. Genes Cancer. 1:1100–1114. 2010. View Article : Google Scholar : PubMed/NCBI
14	Xia SS, Zhang GJ, Liu ZL, Tian HP, He Y, Meng CY, Li LF, Wang ZW and Zhou T: MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer cells through a Sp1 negative feedback loop. Oncotarget. 8:36266–36278. 2017. View Article : Google Scholar : PubMed/NCBI
15	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005. View Article : Google Scholar : PubMed/NCBI
16	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005. View Article : Google Scholar : PubMed/NCBI
17	Babashah S and Soleimani M: The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer. 47:1127–1137. 2011. View Article : Google Scholar : PubMed/NCBI
18	Wang L, Gao W, Hu F, Xu Z and Wang F: MicroRNA-874 inhibits cell proliferation and induces apoptosis in human breast cancer by targeting CDK9. FEBS Lett. 588:4527–4535. 2014. View Article : Google Scholar : PubMed/NCBI
19	Nohata N, Hanazawa T, Kikkawa N, Sakurai D, Fujimura L, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nakagawa M, et al: Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma. Br J Cancer. 105:833–841. 2011. View Article : Google Scholar : PubMed/NCBI
20	Nohata N, Hanazawa T, Kinoshita T, Inamine A, Kikkawa N, Itesako T, Yoshino H, Enokida H, Nakagawa M, Okamoto Y and Seki N: Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma. Br J Cancer. 108:1648–1658. 2013. View Article : Google Scholar : PubMed/NCBI
21	Kesanakurti D, Maddirela DR, Chittivelu S, Rao JS and Chetty C: Suppression of tumor cell invasiveness and in vivo tumor growth by microRNA-874 in non-small cell lung cancer. Biochem Biophys Res Commun. 434:627–633. 2013. View Article : Google Scholar : PubMed/NCBI
22	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
23	Mascarenhas JB, Young KP, Littlejohn EL, Yoo BK, Salgia R and Lang D: PAX6 is expressed in pancreatic cancer and actively participates in cancer progression through activation of the MET tyrosine kinase receptor gene. J Biol Chem. 284:27524–27532. 2009. View Article : Google Scholar : PubMed/NCBI
24	Yonemori K, Seki N, Idichi T, Kurahara H, Osako Y, Koshizuka K, Arai T, Okato A, Kita Y, Arigami T, et al: The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: Anti-tumour functions of the microRNA-216 cluster. Oncotarget. 8:70097–70115. 2017. View Article : Google Scholar : PubMed/NCBI
25	Karamitopoulou E, Haemmig S, Baumgartner U, Schlup C, Wartenberg M and Vassella E: MicroRNA dysregulation in the tumor microenvironment influences the phenotype of pancreatic cancer. Mod Pathol. 30:1116–1125. 2017. View Article : Google Scholar : PubMed/NCBI
26	Kanno S, Nosho K, Ishigami K, Yamamoto I, Koide H, Kurihara H, Mitsuhashi K, Shitani M, Motoya M, Sasaki S, et al: MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer. Carcinogenesis. 38:425–431. 2017. View Article : Google Scholar : PubMed/NCBI
27	Dong D, Gong Y, Zhang D, Bao H and Gu G: miR-874 suppresses the proliferation and metastasis of osteosarcoma by targeting E2F3. Tumour Biol. 37:6447–6455. 2016. View Article : Google Scholar : PubMed/NCBI
28	Han J, Liu Z, Wang N and Pan W: MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein. Oncol Rep. 36:542–550. 2016. View Article : Google Scholar : PubMed/NCBI
29	Zhao B and Dong AS: MiR-874 inhibits cell growth and induces apoptosis by targeting STAT3 in human colorectal cancer cells. Eur Rev Med Pharmacol Sci. 20:269–277. 2016.PubMed/NCBI
30	Que K, Tong Y, Que G, Li L, Lin H, Huang S, Wang R and Tang L: Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal cancer via inactivation of the Hippo signaling pathway. Oncol Rep. 38:3376–3386. 2017.PubMed/NCBI
31	Leong KW, Cheng CW, Wong CM, Ng IO, Kwong YL and Tse E: miR-874-3p is down-regulated in hepatocellular carcinoma and negatively regulates PIN1 expression. Oncotarget. 8:11343–11355. 2017. View Article : Google Scholar : PubMed/NCBI
32	Jiang T, Guan LY, Ye YS, Liu HY and Li R: MiR-874 inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting SOX12. Am J Cancer Res. 7:1310–1321. 2017.PubMed/NCBI
33	Jiang B, Li Z, Zhang W, Wang H, Zhi X, Feng J, Chen Z, Zhu Y, Yang L, Xu H and Xu Z: miR-874 Inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer. J Gastroenterol. 49:1011–1025. 2014. View Article : Google Scholar : PubMed/NCBI
34	Ghosh T, Varshney A, Kumar P, Kaur M, Kumar V, Shekhar R, Devi R, Priyanka P, Khan MM and Saxena S: MicroRNA-874 mediated inhibition of the major G1/S phase cyclin, CCNE1 is lost in osteosarcomas. J Biol Chem. 292:21264–21281. 2017. View Article : Google Scholar : PubMed/NCBI
35	Zhang X, Tang J, Zhi X, Xie K, Wang W, Li Z, Zhu Y, Yang L, Xu H and Xu Z: miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer. Oncotarget. 6:1605–1617. 2015.PubMed/NCBI
36	Georgala PA, Carr CB and Price DJ: The role of Pax6 in forebrain development. Dev Neurobiol. 71:690–709. 2011. View Article : Google Scholar : PubMed/NCBI
37	Hanson IM: PAX6 and congenital eye malformations. Pediatr Res. 54:791–796. 2003. View Article : Google Scholar : PubMed/NCBI
38	Li Y, Li Y, Liu Y, Xie P, Li F and Li G: PAX6, a novel target of microRNA-7, promotes cellular proliferation and invasion in human colorectal cancer cells. Dig Dis Sci. 59:598–606. 2014. View Article : Google Scholar : PubMed/NCBI
39	Li X, Yang L, Shuai T, Piao T and Wang R: MiR-433 inhibits retinoblastoma malignancy by suppressing Notch1 and PAX6 expression. Biomed Pharmacother. 82:247–255. 2016. View Article : Google Scholar : PubMed/NCBI
40	Xia X, Yin W, Zhang X, Yu X, Wang C, Xu S, Feng W and Yang H: PAX6 overexpression is associated with the poor prognosis of invasive ductal breast cancer. Oncol Lett. 10:1501–1506. 2015. View Article : Google Scholar : PubMed/NCBI
41	Zhao X, Yue W, Zhang L, Ma L, Jia W, Qian Z, Zhang C and Wang Y: Downregulation of PAX6 by shRNA inhibits proliferation and cell cycle progression of human non-small cell lung cancer cell lines. PLoS One. 9:e857382014. View Article : Google Scholar : PubMed/NCBI
42	Zou Q, Yi W, Huang J, Fu F, Chen G and Zhong D: MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells. Exp Ther Med. 14:1198–1204. 2017. View Article : Google Scholar : PubMed/NCBI