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Gene Review

LIN28B  -  lin-28 homolog B (C. elegans)

Homo sapiens

Synonyms: CSDD2, FLJ16517, Lin-28B, Protein lin-28 homolog B
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High impact information on LIN28B

  • Gene is located on chromosome 6, and open reading frame encodes 250 amino acids
  • Induced expression of exogenous LIN28B in a tet-off cell line promoted cancer cell proliferation [1].
  • Here we report the cloning and characterization of a novel gene, lin-28 homolog B (LIN28B), which is overexpressed in hepatocellular carcinoma [1].
  • Interestingly, the segment of the unusually long 3'UTR of LIN28B contains complementary sites to let-7 microRNA of mammals [1].
  • Similar with lin-28 proteins, LIN28B conserves a cold shock domain and a pair of CCHC zinc finger domains [1].
  • Ectopic expression of LIN28B in human adult CD34+ HSPCs can mediate expression of fetal hemoglobin in erythroblasts and production of fetal-like erythrocytes from adult human erythroblasts ex vivo [2].
  • a genome-wide association study of 2,817 neuroblastoma cases and 7,473 controls identified an intronic SNP within LIN28B (rs17065417; combined P = 1.2 × 10−8; odds ratio 1.38, 95% CI 1.23–1.54); the rs17065417 risk allele correlates with increased LIN28B expression, decreased expression of let-7 miRNAs and is associated with advanced neuroblastoma and poor prognosis [3].
  • LIN28B genomic amplification and over expression is associated with high-risk pediatric neuroblastoma, and its poor prognosis; mechanisticallylet-7 miRNA expression is suppressed post-transcriptionally, whereas MYCN translation is enhanced [4]

Analytical, diagnostic and therapeutic context of LIN28B

  • By western blot analysis using a polyclonal antibody against LIN28B, a short LIN28B isoform was also identified in non-tumor liver tissue and fetal liver [1].
  • By RT-PCR, LIN28B is expressed in human CD34+ umbilical cord blood, fetal liver, fetal thymus and fetal spleen [5]
  • LIN28B-mediated reactivation of fetal hemoglobin presents a novel therapeutic avenue for treating sickle cell disease and β-thalassemias [2].
  • Described within international patent application for Method of Increasing the Amount of Fetal Hemoglobin in a Cell and/or Mammal (# PCT/US2013/067811 filed October 31, 2013)
  • quantitative Western blotting of LIN28B protein determined that there are ∼650,000 and ∼160,000 molecules per cell in K562 and HEK293 lines, respectively  [6]

Regulation by LIN28B

  • Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) of LIN28B in HEK293 cells identified ∼3000 mRNAs that included HMGA2, IGF2BP1, CBX5 and LIN28B itself  [6] [7]
  • Interestingly, LIN28B auto regulates itself by binding to its own mRNA at seven positions, and promoting translation into protein  [6]
  • Binding of LIN28B to the loop of let-7 pre-miRNAs, recruits TUT4 and TUT7 (encoded by ZCCHC11 and ZCCHC6, respectively) and results in 3' terminal oligo-uridylation  [8] [9] [10], followed by 3'->5' exonucleolysis by DIS3L2  [11] [12]


  1. Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Guo, Y., Chen, Y., Ito, H., Watanabe, A., Ge, X., Kodama, T., Aburatani, H. Gene (2006) [Pubmed]
  2. LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo. Lee, Y.T., de Vasconcellos, J.F., Yuan, J., Byrnes, C., Noh, S.J., Meier, E.R., Kim, K.S., Rabel, A., Kaushal, M., Muljo, S.A., Miller, J.L. Blood. (2013) [Pubmed]
  3. Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. Diskin, S.J., Capasso, M., Schnepp, R.W., Cole, K.A., Attiyeh, E.F., Hou, C., Diamond, M., Carpenter, E.L., Winter, C., Lee, H., Jagannathan, J., Latorre, V., Iolascon, A., Hakonarson, H., Devoto, M., Maris, J.M. Nat. Genet. (2012) [Pubmed]
  4. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Molenaar, J.J., Domingo-Fernández, R., Ebus, M.E., Lindner, S., Koster, J., Drabek, K., Mestdagh, P., van Sluis, P., Valentijn, L.J., van Nes, J., Broekmans, M., Haneveld, F., Volckmann, R., Bray, I., Heukamp, L., Sprüssel, A., Thor, T., Kieckbusch, K., Klein-Hitpass, L., Fischer, M., Vandesompele, J., Schramm, A., van Noesel, M.M., Varesio, L., Speleman, F., Eggert, A., Stallings, R.L., Caron, H.N., Versteeg, R., Schulte, J.H. Nat. Genet. (2012) [Pubmed]
  5. Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis. Yuan, J., Nguyen, C.K., Liu, X., Kanellopoulou, C., Muljo, S.A. Science. (2012) [Pubmed]
  6. Identification of mRNAs bound and regulated by human LIN28 proteins and molecular requirements for RNA recognition. Hafner, M., Max, K.E., Bandaru, P., Morozov, P., Gerstberger, S., Brown, M., Molina, H., Tuschl, T. RNA. (2013) [Pubmed]
  7. Identification of LIN28B-bound mRNAs reveals features of target recognition and regulation. Graf, R., Munschauer, M., Mastrobuoni, G., Mayr, F., Heinemann, U., Kempa, S., Rajewsky, N., Landthaler, M. RNA. Biol. (2013) [Pubmed]
  8. Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). Thornton, J.E., Chang, H.M., Piskounova, E., Gregory, R.I. RNA. (2012) [Pubmed]
  9. Uridylation by TUT4 and TUT7 marks mRNA for degradation. Lim, J., Ha, M., Chang, H., Kwon, S.C., Simanshu, D.K., Patel, D.J., Kim, V.N. Cell. (2014) [Pubmed]
  10. Selective microRNA uridylation by Zcchc6 (TUT7) and Zcchc11 (TUT4). Thornton, J.E., Du, P., Jing, L., Sjekloca, L., Lin, S., Grossi, E., Sliz, P., Zon, L.I., Gregory, R.I. Nucleic. Acids. Res. (2014) [Pubmed]
  11. A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway. Chang, H.M., Triboulet, R., Thornton, J.E., Gregory, R.I. Nature. (2013) [Pubmed]
  12. Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs. Ustianenko, D., Hrossova, D., Potesil, D., Chalupnikova, K., Hrazdilova, K., Pachernik, J., Cetkovska, K., Uldrijan, S., Zdrahal, Z., Vanacova, S. RNA. (2013) [Pubmed]
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