microRNA-based cancer cell reprogramming technology (Review)

Nishikawa,Shimpei; Ishii,Hideshi; Haraguchi,Naotsugu; Kano,Yoshihiro; Fukusumi,Takahito; Ohta,Katsuya; Ozaki,Miyuki; Dewi,Dyah Laksmi; Sakai,Daisuke; Satoh,Taroh; Nagano,Hiroaki; Doki,Yuichiro; Mori,Masaki

doi:10.3892/etm.2012.558

microRNA-based cancer cell reprogramming technology (Review)

Authors:
- Shimpei Nishikawa
- Hideshi Ishii
- Naotsugu Haraguchi
- Yoshihiro Kano
- Takahito Fukusumi
- Katsuya Ohta
- Miyuki Ozaki
- Dyah Laksmi Dewi
- Daisuke Sakai
- Taroh Satoh
- Hiroaki Nagano
- Yuichiro Doki
- Masaki Mori
View Affiliations

Affiliations: Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan, Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan
Published online on: April 23, 2012 https://doi.org/10.3892/etm.2012.558
Pages: 8-14

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Abstract

Epigenetic modifications play crucial roles in cancer initiation and development. Complete reprogramming can be achieved through the introduction of defined biological factors such as Oct4, Sox2, Klf4, and cMyc into mouse and human fibroblasts. Introduction of these transcription factors resulted in the modification of malignant phenotype behavior. Recent studies have shown that human and mouse somatic cells can be reprogrammed to become induced pluripotent stem cells using forced expression of microRNAs, which completely eliminates the need for ectopic protein expression. Considering the usefulness of RNA molecules, microRNA-based reprogramming technology may have future applications in regenerative and cancer medicine.

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1	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
2	John B, Enright AJ, Aravin A, Tuschl T, Sander C and Marks DS: Human MicroRNA targets. PLoS Biol. 2:e3632004. View Article : Google Scholar
3	Houbaviy HB, Murray MF and Sharp PA: Embryonic stem cell-specific microRNAs. Dev Cell. 5:351–358. 2003. View Article : Google Scholar : PubMed/NCBI
4	Lim LP, Glasner ME, Yekta S, Burge CB and Bartel DP: Vertebrate microRNA genes. Science. 299:15402003. View Article : Google Scholar : PubMed/NCBI
5	Leung AK and Sharp PA: MicroRNA functions in stress responses. Mol Cell. 40:205–215. 2010. View Article : Google Scholar : PubMed/NCBI
6	Marsit CJ, Eddy K and Kelsey KT: MicroRNA responses to cellular stress. Cancer Res. 66:10843–10848. 2006. View Article : Google Scholar : PubMed/NCBI
7	Ng HH and Surani MA: The transcriptional and signalling networks of pluripotency. Nat Cell Biol. 13:490–496. 2011. View Article : Google Scholar : PubMed/NCBI
8	Calin GA, Dumitru CD, Shimizu M, et al: Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 99:15524–15529. 2002. View Article : Google Scholar : PubMed/NCBI
9	Calin GA, Ferracin M, Cimmino A, et al: A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 353:1793–1801. 2005. View Article : Google Scholar : PubMed/NCBI
10	Cerchia L and De Franciscis V: Noncoding RNAs in cancer medicine. J Biomed Biotechnol. 2006:1–8. 2006. View Article : Google Scholar
11	Cummins JM, He Y, Leary RJ, et al: The colorectal microRNAome. Proc Natl Acad Sci USA. 103:3687–3692. 2006. View Article : Google Scholar : PubMed/NCBI
12	Wijnhoven B, Michael MZ and Watson DI: MicroRNAs and cancer. Br J Surg. 94:23–30. 2007. View Article : Google Scholar
13	Davis RL, Weintraub H and Lassar AB: Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 51:987–1000. 1987. View Article : Google Scholar : PubMed/NCBI
14	Xie H, Ye M, Feng R and Graf T: Stepwise reprogramming of B cells into macrophages. Cell. 117:663–676. 2004. View Article : Google Scholar : PubMed/NCBI
15	Zhou Q, Brown J, Kanarek A, Rajagopal J and Melton DA: In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 455:627–632. 2008. View Article : Google Scholar : PubMed/NCBI
16	French SW, Hoyer KK, Shen RR and Teitell MA: Transdifferentiation and nuclear reprogramming in hematopoietic development and neoplasia. Immunol Rev. 187:22–39. 2002. View Article : Google Scholar : PubMed/NCBI
17	Ungefroren H and Fändrich F: The programmable cell of monocytic origin (PCMO): a potential adult stem/progenitor cell source for the generation of islet cells. Adv Exp Med Biol. 654:667–682. 2010.PubMed/NCBI
18	Takahashi K and Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676. 2006. View Article : Google Scholar : PubMed/NCBI
19	Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K and Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872. 2007. View Article : Google Scholar
20	Yamanaka S: Elite and stochastic models for induced pluripotent stem cell generation. Nature. 460:49–52. 2009. View Article : Google Scholar : PubMed/NCBI
21	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar
22	McKenna ES and Roberts CW: Epigenetics and cancer without genomic instability. Cell Cycle. 8:23–26. 2009. View Article : Google Scholar : PubMed/NCBI
23	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
24	Rodríguez-Paredes M and Esteller M: Cancer epigenetics reaches mainstream oncology. Nat Med. 17:330–339. 2011.
25	Cavenee W, Dryja TP, Phillips RA, et al: Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature. 305:779–784. 1983. View Article : Google Scholar : PubMed/NCBI
26	Weinberg R: Tumor suppressor genes. Science. 254:1138–1146. 1991. View Article : Google Scholar : PubMed/NCBI
27	Weinberg RA: The retinoblastoma protein and cell cycle control. Cell. 81:323–330. 1995. View Article : Google Scholar : PubMed/NCBI
28	Wang JY: Cellular responses to DNA damage. Curr Opin Cell Biol. 10:240–247. 1998. View Article : Google Scholar : PubMed/NCBI
29	Solinas G, Marchesi F, Garlanda C, Mantovani A and Allavena P: Inflammation-mediated promotion of invasion and metastasis. Cancer Metastasis Rev. 29:243–248. 2010. View Article : Google Scholar : PubMed/NCBI
30	Vogelstein B and Kinzler KW: The multistep nature of cancer. Trends Genet. 9:138–141. 1993. View Article : Google Scholar : PubMed/NCBI
31	Bonavia R, Inda MD, Cavenee WK and Furnari FB: Heterogeneity maintenance in glioblastoma: a social network. Cancer Res. 71:4055–4060. 2011. View Article : Google Scholar : PubMed/NCBI
32	Miyoshi N, Ishii H, Nagai K, et al: Defined factors induce reprogramming of gastrointestinal cancer cells. Proc Natl Acad Sci USA. 107:40–45. 2010. View Article : Google Scholar : PubMed/NCBI
33	Friedlander SYG, Chu GC, Snyder EL, et al: Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell. 16:379–389. 2009. View Article : Google Scholar : PubMed/NCBI
34	Orkin SH and Hochedlinger K: Chromatin connections to pluripotency and cellular reprogramming. Cell. 145:835–850. 2011. View Article : Google Scholar : PubMed/NCBI
35	Gurdon JB and Wilmut I: Nuclear transfer to eggs and oocytes. Cold Spring Harb Perspect Biol. 3:1–14. 2011. View Article : Google Scholar
36	Maekawa M, Yamaguchi K, Nakamura T, et al: Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature. 474:225–229. 2011. View Article : Google Scholar : PubMed/NCBI
37	Nilsen TW: Endo-siRNAs: Yet another layer of complexity in RNA silencing. Nat Struct Mol Biol. 15:546–548. 2008. View Article : Google Scholar : PubMed/NCBI
38	Golden DE, Gerbasi VR and Sontheimer EJ: An inside job for siRNAs. Mol Cell. 31:309–312. 2008. View Article : Google Scholar : PubMed/NCBI
39	Okamura K and Lai EC: Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol. 9:673–678. 2008. View Article : Google Scholar : PubMed/NCBI
40	Suh N and Blelloch R: Small RNAs in early mammalian development: from gametes to gastrulation. Development. 138:1653–1661. 2011. View Article : Google Scholar : PubMed/NCBI
41	Watanabe T, Totoki Y, Toyoda A, et al: Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature. 453:539–543. 2008. View Article : Google Scholar : PubMed/NCBI
42	Watanabe T, Tomizawa S, Mitsuya K, et al: Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science. 332:848–852. 2011. View Article : Google Scholar : PubMed/NCBI
43	Song R, Hennig GW, Wu Q, Jose C, Zheng H and Yan W: Male germ cells express abundant endogenous siRNAs. Proc Natl Acad Sci USA. 108:13159–13164. 2011. View Article : Google Scholar : PubMed/NCBI
44	Suh N, Baehner L, Moltzahn F, Melton C, Shenoy A, Chen J and Blelloch R: MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr Biol. 20:271–277. 2010. View Article : Google Scholar : PubMed/NCBI
45	Ma J, Flemr M, Stein P, et al: MicroRNA activity is suppressed in mouse oocytes. Curr Biol. 20:265–270. 2010. View Article : Google Scholar : PubMed/NCBI
46	Anokye-Danso F, Trivedi CM, Juhr D, et al: Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell. 8:376–388. 2011. View Article : Google Scholar : PubMed/NCBI
47	Miyoshi N, Ishii H, Nagano H, et al: Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell. 8:633–638. 2011. View Article : Google Scholar : PubMed/NCBI
48	Lin SL, Chang DC, Chang-Lin S, Lin CH, Wu DT, Chen DT and Ying SY: Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA. 14:2115–2124. 2008. View Article : Google Scholar : PubMed/NCBI
49	Lin SL, Chang DC, Ying SY, Leu D and Wu DT: MicroRNA miR-302 inhibits the tumorigenicity of human pluripotent stem cells by coordinate suppression of the CDK2 and CDK4/6 cell cycle pathways. Cancer Res. 70:9473–9482. 2010. View Article : Google Scholar : PubMed/NCBI
50	Sozzi G, Huebner K and Croce CM: FHIT in human cancer. Adv Cancer Res. 74:141–166. 1998. View Article : Google Scholar
51	Huebner K and Croce CM: FRA3B and other common fragile sites: the weakest link. Nat Rev Cancer. 1:214–221. 2001. View Article : Google Scholar : PubMed/NCBI
52	Arlt MF, Casper AM and Glover TW: Common fragile sites. Cytogenet Genome Res. 100:92–100. 2003. View Article : Google Scholar
53	Cimprich KA: Fragile sites: breaking up over a slowdown. Curr Biol. 13:R231–R233. 2003. View Article : Google Scholar : PubMed/NCBI
54	Durkin SG and Glover TW: Chromosome fragile sites. Annu Rev Genet. 41:169–192. 2007. View Article : Google Scholar
55	Sutherland GR: Rare fragile sites. Cytogenet Genome Res. 100:77–84. 2003. View Article : Google Scholar
56	Croce CM, Sozzi G and Huebner K: Role of FHIT in human cancer. J Clin Oncol. 17:1618–1624. 1999.PubMed/NCBI
57	Dillon LW, Burrow AA and Wang YH: DNA instability at chromosomal fragile sites in cancer. Curr Genomics. 11:326–337. 2010. View Article : Google Scholar : PubMed/NCBI
58	Casper AM, Nghiem P, Arlt MF and Glover TW: ATR regulates fragile site stability. Cell. 111:779–789. 2002. View Article : Google Scholar : PubMed/NCBI
59	Cirombella R, Montrone G, Stoppacciaro A, et al: Fhit loss in lung preneoplasia: relation to DNA damage response checkpoint activation. Cancer Lett. 291:230–236. 2010. View Article : Google Scholar : PubMed/NCBI
60	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
61	Hu B, Wang H, Wang X, et al: Fhit and CHK1 have opposing effects on homologous recombination repair. Cancer Res. 65:8613–8616. 2005. View Article : Google Scholar : PubMed/NCBI
62	Ishii H, Mimori K, Inoue H, et al: Fhit modulates the DNA damage checkpoint response. Cancer Res. 66:11287–11292. 2006. View Article : Google Scholar : PubMed/NCBI
63	Okumura H, Ishii H, Pichiorri F, Croce CM, Mori M and Huebner K: Fragile gene product, Fhit, in oxidative and replicative stress responses. Cancer Sci. 100:1145–1150. 2009. View Article : Google Scholar : PubMed/NCBI
64	Ishii H, Mimori K, Ishikawa K, et al: Fhit-deficient hematopoietic stem cells survive hydroquinone treatment long-term, carrying precancerous alterations. Cancer Res. 68:3662–3670. 2008. View Article : Google Scholar : PubMed/NCBI
65	Rossi S, Sevignani C, Nnadi SC, Siracusa LD and Calin GA: Cancer-associated genomic regions (CAGRs) and noncoding RNAs: bioinformatics and therapeutic implications. Mamm Genome. 19:526–540. 2008. View Article : Google Scholar : PubMed/NCBI
66	Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S and Sarkar FH: Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance. Drug Resist Updat. 13:109–118. 2010. View Article : Google Scholar : PubMed/NCBI
67	Zimmerman AL and Wu S: MicroRNAs, cancer and cancer stem cells. Cancer Lett. 300:10–19. 2011. View Article : Google Scholar : PubMed/NCBI
68	Cortez MA, Ivan C, Zhou P, Wu X, Ivan M and Calin GA: microRNAs in cancer: from bench to bedside. Adv Cancer Res. 108:113–157. 2010. View Article : Google Scholar : PubMed/NCBI
69	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
70	White NM, Fatoohi E, Metias M, Jung K, Stephan C and Yousef GM: Metastamirs: a stepping stone towards improved cancer management. Nat Rev Clin Oncol. 8:75–84. 2011. View Article : Google Scholar : PubMed/NCBI
71	Kasemeier-Kulesa JC, Teddy JM, Postovit LM, Seftor EA, Seftor RE, Hendrix MJ and Kulesa PM: Reprogramming multipotent tumor cells with the embryonic neural crest micro-environment. Dev Dyn. 237:2657–2666. 2008. View Article : Google Scholar : PubMed/NCBI
72	Wang J, Emadali A, Le Bescont A, Callanan M, Rousseaux S and Khochbin S: Induced malignant genome reprogramming in somatic cells by testis-specific factors. Biochim Biophys Acta. 1809:221–225. 2011. View Article : Google Scholar : PubMed/NCBI
73	Yu J, Vodyanik MA, Smuga-Otto K, et al: Induced pluripotent stem cell lines derived from human somatic cells. Science. 318:1917–1920. 2007. View Article : Google Scholar : PubMed/NCBI
74	Okita K, Nakagawa M, Hyenjong H, Ichisaka T and Yamanaka S: Generation of mouse induced pluripotent stem cells without viral vectors. Science. 322:949–953. 2008. View Article : Google Scholar : PubMed/NCBI
75	Stadtfeld M, Nagaya M, Utikal J, Weir G and Hochedlinger K: Induced pluripotent stem cells generated without viral integration. Science. 322:945–949. 2008. View Article : Google Scholar : PubMed/NCBI
76	Aoi T, Yae K, Nakagawa M, et al: Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science. 321:699–702. 2008. View Article : Google Scholar : PubMed/NCBI
77	Kim JB, Zaehres H, Wu G, Gentile L, et al: Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature. 454:646–650. 2008. View Article : Google Scholar : PubMed/NCBI
78	Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE and Melton DA: Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 26:795–797. 2008. View Article : Google Scholar : PubMed/NCBI
79	Wernig M, Lengner CJ, Hanna J, et al: A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol. 26:916–924. 2008. View Article : Google Scholar : PubMed/NCBI
80	Sun N, Panetta NJ, Gupta DM, et al: Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proc Natl Acad Sci USA. 106:15720–15725. 2009. View Article : Google Scholar : PubMed/NCBI
81	Zhou H, Wu S, Joo JY, et al: Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell. 4:381–384. 2009. View Article : Google Scholar : PubMed/NCBI
82	Shi Y, Do JT, Desponts C, Hahm HS, Schöler HR and Ding S: A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell. 2:525–528. 2008. View Article : Google Scholar : PubMed/NCBI
83	Woltjen K, Michael IP, Mohseni P, et al: piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature. 458:766–770. 2009. View Article : Google Scholar : PubMed/NCBI
84	Judson RL, Babiarz JE, Venere M and Blelloch R: Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat Biotechnol. 27:459–461. 2009. View Article : Google Scholar : PubMed/NCBI
85	Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P and Woltjen K: Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature. 458:771–775. 2009. View Article : Google Scholar : PubMed/NCBI
86	Seki T, Yuasa S, Oda M, et al: Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell. 7:11–14. 2010. View Article : Google Scholar : PubMed/NCBI
87	Warren L, Manos PD, Ahfeldt T, et al: Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 7:618–630. 2010. View Article : Google Scholar : PubMed/NCBI
88	Zhu S, Li W, Zhou H, et al: Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell. 7:651–655. 2010. View Article : Google Scholar : PubMed/NCBI
89	Li Z, Yang CS, Nakashima K and Rana TM: Small RNA-mediated regulation of iPS cell generation. EMBO J. 30:823–834. 2011. View Article : Google Scholar : PubMed/NCBI
90	Subramanyam D, Lamouille S, Judson RL, Liu JY, Bucay N, Derynck R and Blelloch R: Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nat Biotechnol. 29:443–448. 2011. View Article : Google Scholar : PubMed/NCBI
91	Li L, Connelly MC, Wetmore C, Curran T and Morgan JI: Mouse embryos cloned from brain tumors. Cancer Res. 63:2733–2736. 2003.PubMed/NCBI
92	Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L and Jaenisch R: Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev. 18:1875–1885. 2004. View Article : Google Scholar : PubMed/NCBI
93	Blelloch RH, Hochedlinger K, Yamada Y, et al: Nuclear cloning of embryonal carcinoma cells. Proc Natl Acad Sci USA. 101:13985–13990. 2004.PubMed/NCBI
94	Postovit LM, Margaryan NV, Seftor EA, et al: Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells. Proc Natl Acad Sci USA. 105:4329–4334. 2008. View Article : Google Scholar : PubMed/NCBI
95	Utikal J, Maherali N, Kulalert W and Hochedlinger K: Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci. 122:3502–3510. 2009. View Article : Google Scholar : PubMed/NCBI
96	Carette JE, Pruszak J, Varadarajan M, Blomen VA and Gokhale S: Generation of iPSCs from cultured human malignant cells. Blood. 115:4039–4042. 2010. View Article : Google Scholar : PubMed/NCBI
97	Mathieu J, Zhang Z, Zhou W, Wang AJ and Heddleston JM: HIF induces human embryonic stem cell markers in cancer cells. Cancer Res. 71:4640–4652. 2011. View Article : Google Scholar : PubMed/NCBI
98	Allegrucci C, Rushton MD, Dixon JE, et al: Epigenetic reprogramming of breast cancer cells with oocyte extracts. Mol Cancer. 10:72011.PubMed/NCBI