Synthetic miR-145 mimic inhibits multiple myeloma cell growth in vitro and in vivo Retraction in /10.3892/or.2021.8125

Zhang,Qi; Yan,Weiqun; Bai,Yang; Xu,Hao; Fu,Changhao; Zheng,Wenwen; Zhu,Yingqiao; Ma,Jie

doi:10.3892/or.2014.3591

Synthetic miR-145 mimic inhibits multiple myeloma cell growth in vitro and in vivo

Retraction in: /10.3892/or.2021.8125

Authors:
- Qi Zhang
- Weiqun Yan
- Yang Bai
- Hao Xu
- Changhao Fu
- Wenwen Zheng
- Yingqiao Zhu
- Jie Ma
View Affiliations

Affiliations: School of Pharmaceutical Sciences, Jilin University, Jilin, P.R. China, First Hospital of Jilin University, Jilin, P.R. China, Institute of Virology and AIDS Research, First Hospital of Jilin University, Jilin, P.R. China
Published online on: November 5, 2014 https://doi.org/10.3892/or.2014.3591
Pages: 448-456

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

Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic strategies are required to combat this disease. It is well known that tumor‑suppressor microRNA (miRNA) acts as a new potential anticancer agent. Accumulating evidence showed that microRNA-145 (miR-145) is a candidate tumor suppressor miRNA. However, whether miR-145 is involved in the development and progression of MM reamins to be determined. In the present study, we investigated the therapeutic potential of synthetic miR-145 against human MM cells in vitro and in vivo. The results showed that miR-145 was reduced in MM tissues and cell lines. Enforced expression of miR-145 by transfection with miR-145 mimics inhibited cell proliferation, migration, and the invasion abilities of H929 cells. Furthermore, our results demonstrated that the enforced expression of miR-145 in H929 cells profoundly decreased the levels of p-AKT and p-PI3K, which may contribute to some extent to the inhibition of MM cell proliferation and survival. The enforced expression of miR-145 in a xenograft mouse model suppressed tumor growth. In conclusion, our findings suggested that miR-145 may act as a tumor suppressor and contributes to the progression of MM. Additionally, miR-145 mimics is a potential therapeutic agent for the treatment of MM.

View Figures

View References

1	Palumbo A and Anderson K: Multiple myeloma. N Engl J Med. 364:1046–1060. 2011. View Article : Google Scholar : PubMed/NCBI
2	Terpos E, Morgan G, Dimopoulos MA, et al: International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol. 31:2347–2357. 2013. View Article : Google Scholar : PubMed/NCBI
3	Munshi NC and Anderson KC: New strategies in the treatment of multiple myeloma. Clin Cancer Res. 19:3337–3344. 2013. View Article : Google Scholar : PubMed/NCBI
4	Rossi M, Di Martino MT, Morelli E, et al: Molecular targets for the treatment of multiple myeloma. Curr Cancer Drug Targets. 12:757–767. 2012. View Article : Google Scholar : PubMed/NCBI
5	Gao Y, Gao F, Ma JL, Sun WZ and Song LP: The potential clinical applications and prospects of microRNAs in lung cancer. Onco Targets Ther. 7:901–906. 2014. View Article : Google Scholar : PubMed/NCBI
6	Nana-Sinkam SP and Croce CM: Clinical applications for microRNAs in cancer. Clin Pharmacol Ther. 93:98–104. 2013. View Article : Google Scholar
7	Rajkumar SV: Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 86:57–65. 2011. View Article : Google Scholar
8	Lionetti M, Agnelli L, Mosca L, et al: Integrative high-resolution microarray analysis of human myeloma cell lines reveals deregulated miRNA expression associated with allelic imbalances and gene expression profiles. Genes Chromosomes Cancer. 48:521–531. 2009. View Article : Google Scholar : PubMed/NCBI
9	Calin GA, Sevignani C, Dumitru CD, et al: 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
10	Iorio MV and Croce CM: Causes and consequences of microRNA dysregulation. Cancer J. 18:215–222. 2012. View Article : Google Scholar : PubMed/NCBI
11	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
12	Garzon R, Marcucci G and Croce CM: Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 9:775–789. 2010. View Article : Google Scholar : PubMed/NCBI
13	Tagliaferri P, Rossi M, Di Martino MT, et al: Promises and challenges of MicroRNA-based treatment of multiple myeloma. Curr Cancer Drug Targets. 12:838–846. 2012. View Article : Google Scholar : PubMed/NCBI
14	Lionetti M, Biasiolo M, Agnelli L, et al: Identification of microRNA expression patterns and definition of a microRNA/mRNA regulatory network in distinct molecular groups of multiple myeloma. Blood. 114:e20–e26. 2009. View Article : Google Scholar : PubMed/NCBI
15	Calin GA and Croce CM: MicroRNA-cancer connection: the beginning of a new tale. Cancer Res. 66:7390–7394. 2006. View Article : Google Scholar : PubMed/NCBI
16	Chesi M and Bergsagel PL: Molecular pathogenesis of multiple myeloma: basic and clinical updates. Int J Hematol. 97:313–323. 2013. View Article : Google Scholar : PubMed/NCBI
17	Klein B, Seckinger A, Moehler T and Hose D: Molecular pathogenesis of multiple myeloma: chromosomal aberrations, changes in gene expression, cytokine networks, and the bone marrow microenvironment. Recent Results Cancer Res. 183:39–86. 2011. View Article : Google Scholar : PubMed/NCBI
18	Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
19	Pichiorri F, Suh SS, Rocci A, et al: Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development. Cancer Cell. 18:367–381. 2010. View Article : Google Scholar : PubMed/NCBI
20	Noh JH, Chang YG, Kim MG, et al: MiR-145 functions as a tumor suppressor by directly targeting histone deacetylase 2 in liver cancer. Cancer Lett. 335:455–462. 2013. View Article : Google Scholar : PubMed/NCBI
21	Boufraqech M, Zhang L, Jain M, et al: miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3. Endocr Relat Cancer. 21:517–531. 2014. View Article : Google Scholar : PubMed/NCBI
22	Lee SJ, Kim SJ, Seo HH, et al: Over-expression of miR-145 enhances the effectiveness of HSVtk gene therapy for malignant glioma. Cancer Lett. 320:72–80. 2012. View Article : Google Scholar : PubMed/NCBI
23	Cho WC, Chow AS and Au JS: Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation. Eur J Cancer. 45:2197–2206. 2009. View Article : Google Scholar : PubMed/NCBI
24	Chiyomaru T, Enokida H, Tatarano S, et al: miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer. 102:883–891. 2010. View Article : Google Scholar : PubMed/NCBI
25	Zhang J, Guo H, Zhang H, et al: Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene Friend leukemia virus integration 1 gene. Cancer. 117:86–95. 2011. View Article : Google Scholar
26	Spizzo R, Nicoloso MS, Lupini L, et al: miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells. Cell Death Differ. 17:246–254. 2010. View Article : Google Scholar
27	Lin Y, Peng S and Yu H: RNAi-mediated downregulation of NOB1 suppresses the growth and colony-formation ability of human ovarian cancer cells. Med Oncol. 29:311–317. 2012. View Article : Google Scholar
28	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
29	Manikandan J, Aarthi JJ, Kumar SD and Pushparaj PN: Oncomirs: the potential role of non-coding microRNAs in understanding cancer. Bioinformation. 2:330–334. 2008. View Article : Google Scholar : PubMed/NCBI
30	Cordes KR, Sheehy NT, White MP, et al: miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 460:705–710. 2009.PubMed/NCBI
31	Ostenfeld MS, Bramsen JB, Lamy P, et al: miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors. Oncogene. 29:1073–1084. 2010. View Article : Google Scholar
32	Villadsen SB, Bramsen JB, Ostenfeld MS, et al: The miR-143/-145 cluster regulates plasminogen activator inhibitor-1 in bladder cancer. Br J Cancer. 106:366–374. 2012. View Article : Google Scholar :
33	Xu N, Papagiannakopoulos T, Pan G, Thomson JA and Kosik KS: MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 137:647–658. 2009. View Article : Google Scholar : PubMed/NCBI
34	Sachdeva M, Zhu S, Wu F, et al: p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA. 106:3207–3212. 2009. View Article : Google Scholar : PubMed/NCBI
35	Shi B, Sepp-Lorenzino L, Prisco M, Linsley P, deAngelis T and Baserga R: Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem. 282:32582–32590. 2007. View Article : Google Scholar : PubMed/NCBI
36	Sachdeva M and Mo YY: MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res. 70:378–387. 2010. View Article : Google Scholar :
37	Gregersen LH, Jacobsen AB, Frankel LB, Wen J, Krogh A and Lund AH: MicroRNA-145 targets YES and STAT1 in colon cancer cells. PLoS One. 5:e88362010. View Article : Google Scholar : PubMed/NCBI
38	Lu R, Ji Z, Li X, et al: miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma. J Cancer Res Clin Oncol. 140:387–397. 2014. View Article : Google Scholar : PubMed/NCBI
39	Li E, Zhang J, Yuan T and Ma B: miR-145 inhibits osteosarcoma cells proliferation and invasion by targeting ROCK1. Tumour Biol. 35:7645–7650. 2014. View Article : Google Scholar : PubMed/NCBI
40	Xing AY, Wang B, Shi DB, et al: Deregulated expression of miR-145 in manifold human cancer cells. Exp Mol Pathol. 95:91–97. 2013. View Article : Google Scholar : PubMed/NCBI
41	Feng Y, Zhu J, Ou C, et al: MicroRNA-145 inhibits tumour growth and metastasis in colorectal cancer by targeting fascin-1. Br J Cancer. 110:2300–2309. 2014. View Article : Google Scholar : PubMed/NCBI
42	Wang Y, Hu C, Cheng J, et al: MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling. Biochem Biophys Res Commun. 446:1255–1260. 2014. View Article : Google Scholar : PubMed/NCBI
43	Shao Y, Qu Y, Dang S, Yao B and Ji M: MiR-145 inhibits oral squamous cell carcinoma (OSCC) cell growth by targeting c-Myc and Cdk6. Cancer Cell Int. 13:512013. View Article : Google Scholar : PubMed/NCBI
44	Chandramohan V, Jeay S, Pianetti S and Sonenshein GE: Reciprocal control of Forkhead box O 3a and c-Myc via the phosphatidylinositol 3-kinase pathway coordinately regulates p27Kip1 levels. J Immunol. 172:5522–5527. 2004. View Article : Google Scholar : PubMed/NCBI
45	Cheng GZ, Park S, Shu S, et al: Advances of AKT pathway in human oncogenesis and as a target for anti-cancer drug discovery. Curr Cancer Drug Targets. 8:2–6. 2008. View Article : Google Scholar : PubMed/NCBI
46	Medema RH, Kops GJ, Bos JL and Burgering BM: AFX-like Forkhead transcription factors mediate cell cycle regulation by Ras and PKB through p27kip1. Nature. 404:782–787. 2000. View Article : Google Scholar : PubMed/NCBI
47	Roy SK, Srivastava RK and Shankar S: Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J Mol Signal. 5:102010. View Article : Google Scholar : PubMed/NCBI
48	Massague J: G1 cell-cycle control and cancer. Nature. 432:298–306. 2004. View Article : Google Scholar : PubMed/NCBI
49	Maddika S, Ande SR, Panigrahi S, et al: Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat. 10:13–29. 2007. View Article : Google Scholar : PubMed/NCBI
50	Datta SR, Dudek H, Tao X, et al: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:231–241. 1997. View Article : Google Scholar : PubMed/NCBI