Hsa-miR-520d Induces Hepatoma Cells to Form Normal Liver Tissues Via a Stemness-mediated Process

Overview

Journal Sci Rep

Specialty Science

Date 2014 Jan 25

PMID 24458129

Citations 16

Authors

Satoshi Tsuno

Xinhui Wang

Kohei Shomori

Junichi Hasegawa

Norimasa Miura

Affiliations

Soon will be listed here.

Abstract

The human ncRNA gene RGM249 regulates the extent of differentiation of cancer cells and the conversion of 293FT cells to hiPSCs. To identify the factors underlying this process, we investigated the effects of lentivirally inducing miR-520d expression in 293FT and HLF cells in vitro. Subsequently, we evaluated tumor formation in a xenograft model. Transformed HLF cells were Oct4 and Nanog positive within 24 h, showed p53 upregulation and hTERT downregulation, and mostly lost their migration abilities. After lentiviral infection, the cells were intraperitoneally injected into mice, resulting in benign teratomas (6%), the absence of tumors (87%) or differentiation into benign liver tissues (7%) at the injection site after 1 month. We are the first to demonstrate the loss of malignant properties in cancer cells in vivo through the expression of a single microRNA (miRNA). This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like cells. The regulation of malignancy by miR-520d appears to be through the conversion of cancer cells to normal stem cells, maintaining p53 upregulation.

Citing Articles

Gupta H, Youn G, Han S, Shin M, Yoon S, Han D J Clin Med. 2019; 8(6).

PMID: 31212896 PMC: 6616969. DOI: 10.3390/jcm8060862.

miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives.

Miura N, Ishihara Y, Miura Y, Kimoto M, Miura K BMC Cancer. 2019; 19(1):587.

PMID: 31202279 PMC: 6570841. DOI: 10.1186/s12885-019-5786-y.

Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.

Ulivi P, Canale M, Passardi A, Marisi G, Valgiusti M, Frassineti G Int J Mol Sci. 2018; 19(1).

PMID: 29361687 PMC: 5796251. DOI: 10.3390/ijms19010307.

miR-524-5p of the primate-specific C19MC miRNA cluster targets TP53IPN1- and EMT-associated genes to regulate cellular reprogramming.

Nguyen P, Choo K, Huang C, Sugii S, Cheong S, Kamarul T Stem Cell Res Ther. 2017; 8(1):214.

PMID: 28962647 PMC: 5622517. DOI: 10.1186/s13287-017-0666-3.

Genome-wide miRNA response to anacardic acid in breast cancer cells.

Schultz D, Muluhngwi P, Alizadeh-Rad N, Green M, Rouchka E, Waigel S PLoS One. 2017; 12(9):e0184471.

PMID: 28886127 PMC: 5590942. DOI: 10.1371/journal.pone.0184471.

References

Calin G, Liu C, Sevignani C, Ferracin M, Felli N, Dumitru C . MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A. 2004; 101(32):11755-60. PMC: 511048. DOI: 10.1073/pnas.0404432101. View

Zhang D, Zhao T, Ang H, Chong P, Saiki R, Igarashi K . AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells. Genes Dev. 2012; 26(5):461-73. PMC: 3305984. DOI: 10.1101/gad.182998.111. View

Sand M, Gambichler T, Skrygan M, Sand D, Scola N, Altmeyer P . Expression levels of the microRNA processing enzymes Drosha and dicer in epithelial skin cancer. Cancer Invest. 2010; 28(6):649-53. DOI: 10.3109/07357901003630918. View

Miura N, Sato R, Tsukamoto T, Shimizu M, Kabashima H, Takeda M . A noncoding RNA gene on chromosome 10p15.3 may function upstream of hTERT. BMC Mol Biol. 2009; 10:5. PMC: 2661890. DOI: 10.1186/1471-2199-10-5. View

Ohashi Y, Hirayama A, Ishikawa T, Nakamura S, Shimizu K, Ueno Y . Depiction of metabolome changes in histidine-starved Escherichia coli by CE-TOFMS. Mol Biosyst. 2008; 4(2):135-47. DOI: 10.1039/b714176a. View

Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H . Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res. 2009; 69(11):4918-25. DOI: 10.1158/0008-5472.CAN-08-4806. View

Klukas C, Schreiber F . Integration of -omics data and networks for biomedical research with VANTED. J Integr Bioinform. 2010; 7(2):112. DOI: 10.2390/biecoll-jib-2010-112. View

Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S . MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology. 2008; 47(6):1955-63. DOI: 10.1002/hep.22256. View

Gunaratne P . Embryonic stem cell microRNAs: defining factors in induced pluripotent (iPS) and cancer (CSC) stem cells?. Curr Stem Cell Res Ther. 2009; 4(3):168-77. DOI: 10.2174/157488809789057400. View

10.

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K . Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007; 131(5):861-72. DOI: 10.1016/j.cell.2007.11.019. View

11.

Nascimento E, Cox C, MacArthur S, Hussain S, Trotter M, Blanco S . The opposing transcriptional functions of Sin3a and c-Myc are required to maintain tissue homeostasis. Nat Cell Biol. 2011; 13(12):1395-405. PMC: 3242072. DOI: 10.1038/ncb2385. View

12.

Lowery A, Miller N, Devaney A, McNeill R, Davoren P, Lemetre C . MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 2009; 11(3):R27. PMC: 2716495. DOI: 10.1186/bcr2257. View

13.

Tsai C, Su P, Huang Y, Yew T, Hung S . Oct4 and Nanog directly regulate Dnmt1 to maintain self-renewal and undifferentiated state in mesenchymal stem cells. Mol Cell. 2012; 47(2):169-82. DOI: 10.1016/j.molcel.2012.06.020. View

14.

Henry J, Park J, Jiang J, Kim J, Nagorney D, Roberts L . miR-199a-3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines. Biochem Biophys Res Commun. 2010; 403(1):120-5. PMC: 3039123. DOI: 10.1016/j.bbrc.2010.10.130. View

15.

Panopoulos A, Yanes O, Ruiz S, Kida Y, Diep D, Tautenhahn R . The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 2011; 22(1):168-77. PMC: 3252494. DOI: 10.1038/cr.2011.177. View

16.

Zeng Y, Cullen B . Sequence requirements for micro RNA processing and function in human cells. RNA. 2003; 9(1):112-23. PMC: 1370375. DOI: 10.1261/rna.2780503. View

17.

Plaisant M, Fontaine C, Cousin W, Rochet N, Dani C, Peraldi P . Activation of hedgehog signaling inhibits osteoblast differentiation of human mesenchymal stem cells. Stem Cells. 2008; 27(3):703-13. DOI: 10.1634/stemcells.2008-0888. View

18.

Yehezkel S, Rebibo-Sabbah A, Segev Y, Tzukerman M, Shaked R, Huber I . Reprogramming of telomeric regions during the generation of human induced pluripotent stem cells and subsequent differentiation into fibroblast-like derivatives. Epigenetics. 2010; 6(1):63-75. PMC: 3052915. DOI: 10.4161/epi.6.1.13390. View

19.

Okita K, Ichisaka T, Yamanaka S . Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448(7151):313-7. DOI: 10.1038/nature05934. View

20.

Miura N, Nakamura H, Sato R, Tsukamoto T, Harada T, Takahashi S . Clinical usefulness of serum telomerase reverse transcriptase (hTERT) mRNA and epidermal growth factor receptor (EGFR) mRNA as a novel tumor marker for lung cancer. Cancer Sci. 2006; 97(12):1366-73. PMC: 11160089. DOI: 10.1111/j.1349-7006.2006.00342.x. View