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; mechanistically, let-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]

References