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Lin28: an emerging important oncogene connecting several aspects of cancer

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Tumor Biology

Abstract

RNA-binding protein Lin28 was originally found as a heterochronic gene which played a significant role in the development of Caenorhabditis elegans. The tumor suppressor let-7 is a downstream target of Lin28, which has a wide variety of target genes which are involved in many aspects of cellular activities. By inhibition of let-7 and directly binding the target RNAs, Lin28 plays an important role in different biological and pathological processes including differentiation, metabolism, proliferation, pluripotency, and tumorigenesis. Overexpression of Lin28 has been reported in several kinds of cancers and is correlated with poor outcomes. It has been shown that Lin28 could affect the progression of cancers in several ways, such as promoting proliferation, increasing glucose metabolism, and inducing epithelial-mesenchymal transition (EMT) and cancer stem cells. Decrease of Lin28 expression or reactivation of let-7 in cancer cells could induce a reverse effect, indicating their therapeutic values in developing novel strategies for cancer treatment. Here, we will overview the regulatory mechanisms and functions of Lin28 in cancers.

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References

  1. Mitchell SF, Parker R. Principles and properties of eukaryotic mRNPs. Mol Cell. 2014;54(4):547–58.

    Article  CAS  PubMed  Google Scholar 

  2. Wurth L, Gebauer F. RNA-binding proteins, multifaceted translational regulators in cancer. Biochim Biophys Acta. 2015;1849(7):881–6.

    Article  CAS  PubMed  Google Scholar 

  3. Moss EG, Lee RC, Ambros V. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell. 1997;88(5):637–46.

    Article  CAS  PubMed  Google Scholar 

  4. Ambros V, Horvitz HR. Heterochronic mutants of the nematode Caenorhabditis elegans. Science. 1984;226(4673):409–16.

    Article  CAS  PubMed  Google Scholar 

  5. Zhou J, Ng SB, Chng WJ. LIN28/LIN28B: an emerging oncogenic driver in cancer stem cells. Int J Biochem Cell Biol. 2013;45(5):973–8.

    Article  CAS  PubMed  Google Scholar 

  6. Yang DH, Moss EG. Temporally regulated expression of Lin-28 in diverse tissues of the developing mouse. Gene Expr Patterns. 2003;3(6):719–26.

    Article  CAS  PubMed  Google Scholar 

  7. Balzer E, Moss EG. Localization of the developmental timing regulator Lin28 to mRNP complexes, P-bodies and stress granules. RNA Biol. 2007;4(1):16–25.

    Article  CAS  PubMed  Google Scholar 

  8. Hafner M, Max KE, Bandaru P, Morozov P, Gerstberger S, Brown M, et al. Identification of mRNAs bound and regulated by human LIN28 proteins and molecular requirements for RNA recognition. RNA. 2013;19(5):613–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Piskounova E, Polytarchou C, Thornton JE, LaPierre RJ, Pothoulakis C, Hagan JP, et al. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell. 2011;147(5):1066–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gaytan F, Sangiao-Alvarellos S, Manfredi-Lozano M, Garcia-Galiano D, Ruiz-Pino F, Romero-Ruiz A, et al. Distinct expression patterns predict differential roles of the miRNA-binding proteins, Lin28 and Lin28b, in the mouse testis: studies during postnatal development and in a model of hypogonadotropic hypogonadism. Endocrinology. 2013;154(3):1321–36.

    Article  CAS  PubMed  Google Scholar 

  11. Kolenda T, Przybyla W, Teresiak A, Mackiewicz A, Lamperska KM. The mystery of let-7d - a small RNA with great power. Contemp Oncol (Pozn). 2014;18(5):293–301.

    Google Scholar 

  12. Newman MA, Thomson JM, Hammond SM. Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA. 2008;14(8):1539–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Heo I, Joo C, Kim YK, Ha M, Yoon MJ, Cho J, et al. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell. 2009;138(4):696–708.

    Article  CAS  PubMed  Google Scholar 

  14. Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. Lin28 mediates the terminal uridylation of let-7 precursor microRNA. Mol Cell. 2008;32(2):276–84.

    Article  CAS  PubMed  Google Scholar 

  15. Lim J, Ha M, Chang H, Kwon SC, Simanshu DK, Patel DJ, et al. Uridylation by TUT4 and TUT7 marks mRNA for degradation. Cell. 2014;159(6):1365–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ustianenko D, Hrossova D, Potesil D, Chalupnikova K, Hrazdilova K, Pachernik J, et al. Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs. RNA. 2013;19(12):1632–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yang X, Lin X, Zhong X, Kaur S, Li N, Liang S, et al. Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells. Cancer Res. 2010;70(22):9463–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl EE, Nitsch R, et al. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol. 2008;10(8):987–93.

    Article  CAS  PubMed  Google Scholar 

  19. Peng S, Chen LL, Lei XX, Yang L, Lin H, Carmichael GG, et al. Genome-wide studies reveal that Lin28 enhances the translation of genes important for growth and survival of human embryonic stem cells. Stem Cells. 2011;29(3):496–504.

    Article  CAS  PubMed  Google Scholar 

  20. Shyh-Chang N, Daley GQ. Lin28: primal regulator of growth and metabolism in stem cells. Cell Stem Cell. 2013;12(4):395–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wilbert ML, Huelga SC, Kapeli K, Stark TJ, Liang TY, Chen SX, et al. LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance. Mol Cell. 2012;48(2):195–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zisoulis DG, Kai ZS, Chang RK, Pasquinelli AE. Autoregulation of microRNA biogenesis by let-7 and Argonaute. Nature. 2012;486(7404):541–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Urbach A, Yermalovich A, Zhang J, Spina CS, Zhu H, Perez-Atayde AR, et al. Lin28 sustains early renal progenitors and induces Wilms tumor. Genes Dev. 2014;28(9):971–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Molenaar JJ, Domingo-Fernandez R, Ebus ME, Lindner S, Koster J, Drabek K, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet. 2012;44(11):1199–206.

    Article  CAS  PubMed  Google Scholar 

  25. Nguyen LH, Robinton DA, Seligson MT, Wu L, Li L, Rakheja D, et al. Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models. Cancer Cell. 2014;26(2):248–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. You X, Liu F, Zhang T, Lv N, Liu Q, Shan C, et al. Hepatitis B virus X protein upregulates Lin28A/Lin28B through Sp-1/c-Myc to enhance the proliferation of hepatoma cells. Oncogene. 2014;33(4):449–60.

    Article  CAS  PubMed  Google Scholar 

  27. Wang L, Zhang LF, Wu J, Xu SJ, Xu YY, Li D, et al. IL-1beta-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis. Cancer Res. 2014;74(17):4720–30.

    Article  CAS  PubMed  Google Scholar 

  28. Rakheja D, Chen KS, Liu Y, Shukla AA, Schmid V, Chang TC, et al. Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours. Nat Commun. 2014;2:4802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Qin R, Zhou J, Chen C, Xu T, Yan Y, Ma Y, et al. LIN28 is involved in glioma carcinogenesis and predicts outcomes of glioblastoma multiforme patients. PLoS One. 2014;9(1), e86446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Xie R, Wang Y, Nie W, Huang W, Song W, Wang Z, et al. Lin28B expression correlates with aggressive clinicopathological characteristics in breast invasive ductal carcinoma. Cancer Biother Radiopharm. 2014;29(5):215–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu Y, Li H, Feng J, Cui X, Huang W, Li Y, et al. Lin28 induces epithelial-to-mesenchymal transition and stemness via downregulation of let-7a in breast cancer cells. PLoS One. 2013;8(12):e83083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hu Q, Peng J, Liu W, He X, Cui L, Chen X, et al. Lin28B is a novel prognostic marker in gastric adenocarcinoma. Int J Clin Exp Pathol. 2014;7(8):5083–92.

    PubMed  PubMed Central  Google Scholar 

  33. Li Y, Liu H, Lai C, Du X, Su Z, Gao S. The Lin28/let-7a/c-Myc pathway plays a role in non-muscle invasive bladder cancer. Cell Tissue Res. 2013;354(2):533–41.

    Article  CAS  PubMed  Google Scholar 

  34. Wu T, Jia J, Xiong X, He H, Bu L, Zhao Z, et al. Increased expression of Lin28B associates with poor prognosis in patients with oral squamous cell carcinoma. PLoS One. 2013;8(12):e83869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Murray MJ, Saini HK, Siegler CA, Hanning JE, Barker EM, van Dongen S, et al. LIN28 Expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels. Cancer Res. 2013;73(15):4872–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Peng S, Maihle NJ, Huang Y. Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene. 2010;29(14):2153–9.

    Article  CAS  PubMed  Google Scholar 

  37. Lu L, Katsaros D, Shaverdashvili K, Qian B, Wu Y, de la Longrais IA, et al. Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II. Eur J Cancer. 2009;45(12):2212–8.

    Article  CAS  PubMed  Google Scholar 

  38. Li N, Zhong X, Lin X, Guo J, Zou L, Tanyi JL, et al. Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer. J Biol Chem. 2012;287(21):17386–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sampson VB, Rong NH, Han J, Yang Q, Aris V, Soteropoulos P, et al. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 2007;67(20):9762–70.

    Article  CAS  PubMed  Google Scholar 

  40. Dang CV. Therapeutic targeting of Myc-reprogrammed cancer cell metabolism. Cold Spring Harb Symp Quant Biol. 2011;76:369–74.

    Article  CAS  PubMed  Google Scholar 

  41. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007;21(9):1025–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Boyerinas B, Park SM, Shomron N, Hedegaard MM, Vinther J, Andersen JS, et al. Identification of let-7-regulated oncofetal genes. Cancer Res. 2008;68(8):2587–91.

    Article  CAS  PubMed  Google Scholar 

  43. Deng K, Guo X, Wang H, Xia J. The lncRNA-MYC regulatory network in cancer. Tumour Biol. 2014;35(10):9497–503.

    Article  CAS  PubMed  Google Scholar 

  44. Wang Z, Lin S, Li JJ, Xu Z, Yao H, Zhu X, et al. MYC protein inhibits transcription of the microRNA cluster MC-let-7a-1∼let-7d via noncanonical E-box. J Biol Chem. 2011;286(46):39703–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Buechner J, Tomte E, Haug BH, Henriksen JR, Lokke C, Flaegstad T, et al. Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma. Br J Cancer. 2011;105(2):296–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005;120(5):635–47.

    Article  CAS  PubMed  Google Scholar 

  47. Downward J. Targeting RAS, signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3(1):11–22.

    Article  CAS  PubMed  Google Scholar 

  48. Pallante P, Sepe R, Puca F, Fusco A. High mobility group a proteins as tumor markers. Front Med (Lausanne). 2015;2:15.

    Google Scholar 

  49. Kim CW, Vo MT, Kim HK, Lee HH, Yoon NA, Lee BJ, et al. Ectopic over-expression of tristetraprolin in human cancer cells promotes biogenesis of let-7 by down-regulation of Lin28. Nucleic Acids Res. 2012;40(9):3856–69.

    Article  CAS  PubMed  Google Scholar 

  50. Zhong X, Li N, Liang S, Huang Q, Coukos G, Zhang L. Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells. J Biol Chem. 2010;285(53):41961–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mathews MB, Hershey JW. The translation factor eIF5A and human cancer. Biochim Biophys Acta. 2015;1849(7):836–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lozier AM, Rich ME, Grawe AP, Peck AS, Zhao P, Chang AT, et al. Targeting ornithine decarboxylase reverses the LIN28/Let-7 axis and inhibits glycolytic metabolism in neuroblastoma. Oncotarget. 2015;6(1):196–206.

    PubMed  Google Scholar 

  53. Paz EA, LaFleur B, Gerner EW. Polyamines are oncometabolites that regulate the LIN28/let-7 pathway in colorectal cancer cells. Mol Carcinog. 2014;53 Suppl 1:E96–106.

    Article  CAS  PubMed  Google Scholar 

  54. Grivennikov SI, Karin M. Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev. 2010;20(1):65–71.

    Article  CAS  PubMed  Google Scholar 

  55. Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 microRNA, and IL6 links inflammation to cell transformation. Cell. 2009;139(4):693–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lu J, Tan M, Cai Q. The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett. 2015;356(2 Pt A):156–64.

    Article  CAS  PubMed  Google Scholar 

  58. Zhu H, Shah S, Shyh-Chang N, Shinoda G, Einhorn WS, Viswanathan SR, et al. Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nat Genet. 2010;42(7):626–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shyh-Chang N, Zhu H. Yvanka de Soysa T, Shinoda G, Seligson MT, Tsanov KM et al. Lin28 enhances tissue repair by reprogramming cellular metabolism. Cell. 2013;155(4):778–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Frost RJ, Olson EN. Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs. Proc Natl Acad Sci U S A. 2011;108(52):21075–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Cargnello M, Tcherkezian J, Roux PP. The expanding role of mTOR in cancer cell growth and proliferation. Mutagenesis. 2015;30(2):169–76.

    Article  CAS  PubMed  Google Scholar 

  62. Tsialikas J, Romer-Seibert J. LIN28: roles and regulation in development and beyond. Development. 2015;142(14):2397–404.

    Article  CAS  PubMed  Google Scholar 

  63. Zhu H, Shyh-Chang N, Segre AV, Shinoda G, Shah SP, Einhorn WS, et al. The Lin28/let-7 axis regulates glucose metabolism. Cell. 2011;147(1):81–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dang CV. The interplay between MYC and HIF in the Warburg effect. Ernst Schering Found Symp Proc. 2007;4:35–53.

    Google Scholar 

  65. Ma X, Li C, Sun L, Huang D, Li T, He X, et al. Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1. Nat Commun. 2014;5:5212.

    Article  CAS  PubMed  Google Scholar 

  66. Jin J, Jing W, Lei XX, Feng C, Peng S, Boris-Lawrie K, et al. Evidence that Lin28 stimulates translation by recruiting RNA helicase A to polysomes. Nucleic Acids Res. 2011;39(9):3724–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Qiu C, Ma Y, Wang J, Peng S, Huang Y. Lin28-mediated post-transcriptional regulation of Oct4 expression in human embryonic stem cells. Nucleic Acids Res. 2010;38(4):1240–8.

    Article  CAS  PubMed  Google Scholar 

  68. Xu B, Zhang K, Huang Y. Lin28 modulates cell growth and associates with a subset of cell cycle regulator mRNAs in mouse embryonic stem cells. RNA. 2009;15(3):357–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Spence T, Perotti C, Sin-Chan P, Picard D, Wu W, Singh A, et al. A novel C19MC amplified cell line links Lin28/let-7 to mTOR signaling in embryonal tumor with multilayered rosettes. Neuro Oncol. 2014;16(1):62–71.

    Article  CAS  PubMed  Google Scholar 

  70. van der Pluijm G. Epithelial plasticity, cancer stem cells and bone metastasis formation. Bone. 2011;48(1):37–43.

    Article  CAS  PubMed  Google Scholar 

  71. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wang SS, Jiang J, Liang XH, Tang YL. Links between cancer stem cells and epithelial-mesenchymal transition. Onco Targets Ther. 2015;8:2973–80.

    PubMed  PubMed Central  Google Scholar 

  73. Biddle A, Mackenzie IC. Cancer stem cells and EMT in carcinoma. Cancer Metastasis Rev. 2012. doi:10.1007/s10555-012-9345-0 [doi]

  74. Guo L, Chen C, Shi M, Wang F, Chen X, Diao D, et al. Stat3-coordinated Lin-28-let-7-HMGA2 and miR-200-ZEB1 circuits initiate and maintain oncostatin M-driven epithelial-mesenchymal transition. Oncogene. 2013;32(45):5272–82.

    Article  CAS  PubMed  Google Scholar 

  75. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.

    Article  CAS  PubMed  Google Scholar 

  76. Chien CS, Wang ML, Chu PY, Chang YL, Liu WH, Yu CC, et al. Lin28B/Let-7 regulates expression of Oct4 and Sox2 and reprograms oral squamous cell carcinoma cells to a stem-like state. Cancer Res. 2015;75(12):2553–65.

    Article  CAS  PubMed  Google Scholar 

  77. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jolly MK, Jia D, Boareto M, Mani SA, Pienta KJ, Ben-Jacob E, et al. Coupling the modules of EMT and stemness: a tunable ‘stemness window’ model. Oncotarget. 2015;6(28):25161–74.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Chang CJ, Hsu CC, Chang CH, Tsai LL, Chang YC, Lu SW, et al. Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer. Oncol Rep. 2011;26(4):1003–10.

    CAS  PubMed  Google Scholar 

  80. Li Y, VandenBoom 2nd TG, Kong D, Wang Z, Ali S, Philip PA, et al. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009;69(16):6704–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wang YC, Chen YL, Yuan RH, Pan HW, Yang WC, Hsu HC, et al. Lin-28B expression promotes transformation and invasion in human hepatocellular carcinoma. Carcinogenesis. 2010;31(9):1516–22.

    Article  CAS  PubMed  Google Scholar 

  82. Oh JS, Kim JJ, Byun JY, Kim IA. Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras. Int J Radiat Oncol Biol Phys. 2010;76(1):5–8.

    Article  CAS  PubMed  Google Scholar 

  83. Teng R, Hu Y, Zhou J, Seifer B, Chen Y, Shen J, et al. Overexpression of Lin28 decreases the chemosensitivity of gastric cancer cells to oxaliplatin, paclitaxel, doxorubicin, and fluorouracil in part via microRNA-107. PLoS One. 2015;10(12):e0143716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lv K, Liu L, Wang L, Yu J, Liu X, Cheng Y, et al. Lin28 mediates paclitaxel resistance by modulating p21, Rb and Let-7a miRNA in breast cancer cells. PLoS One. 2012;7(7):e40008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Tian N, Han Z, Li Z, Zhou M, Fan C. Lin28/let-7/Bcl-xL pathway: the underlying mechanism of drug resistance in Hep3B cells. Oncol Rep. 2014;32(3):1050–6.

    CAS  PubMed  Google Scholar 

  86. Yang X, Cai H, Liang Y, Chen L, Wang X, Si R, et al. Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells. Oncol Rep. 2015;33(4):1723–30.

    PubMed  Google Scholar 

  87. Nadiminty N, Tummala R, Lou W, Zhu Y, Shi XB, Zou JX, et al. MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. PLoS One. 2012;7(3), e32832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nadiminty N, Tummala R, Lou W, Zhu Y, Zhang J, Chen X, et al. MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells. J Biol Chem. 2012;287(2):1527–37.

    Article  CAS  PubMed  Google Scholar 

  89. Tummala R, Nadiminty N, Lou W, Zhu Y, Gandour-Edwards R, Chen HW, et al. Lin28 promotes growth of prostate cancer cells and activates the androgen receptor. Am J Pathol. 2013;183(1):288–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Proverbs-Singh T, Feldman JL, Morris MJ, Autio KA, Traina TA. Targeting the androgen receptor in prostate and breast cancer: several new agents in development. Endocr Relat Cancer. 2015;22(3):R87–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wang Q, Zhou J, Guo J, Teng R, Shen J, Huang Y, et al. Lin28 promotes Her2 expression and Lin28/Her2 predicts poorer survival in gastric cancer. Tumour Biol. 2014;35(11):11513–21.

    Article  CAS  PubMed  Google Scholar 

  92. Feng C, Neumeister V, Ma W, Xu J, Lu L, Bordeaux J, et al. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle. 2012;11(13):2486–94.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, 214002, Jiangsu, China

    Hao Wang, Qin Zhao, Kaiyuan Deng, Xiaoqiang Guo & Jiazeng Xia

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Wang, H., Zhao, Q., Deng, K. et al. Lin28: an emerging important oncogene connecting several aspects of cancer. Tumor Biol. 37, 2841–2848 (2016). https://doi.org/10.1007/s13277-015-4759-2

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