Krüppel-Like Factor 10 participates in cervical cancer immunoediting through transcriptional regulation of Pregnancy-Specific Beta-1 Glycoproteins

Marrero-Rodríguez D, Taniguchi-Ponciano K, Subramaniam M, Hawse JR, Pitel KS, Arreola-De la Cruz H, Huerta-Padilla V, Ponce-Navarrete G, Figueroa-Corona MDP, Gomez-Virgilio L, Martinez-Cuevas TI, Mendoza-Rodriguez M, Rodriguez-Esquivel M, Romero-Morelos P, Ramirez-Salcedo J, Baudis M, Meraz-Rios M, Jimenez-Vega F, Salcedo M.

Abstract Cervical cancer (CC) is associated with alterations in immune system balance, which is primarily due to a shift from Th1 to Th2 and the unbalance of Th17/Treg cells. Using in silico DNA copy number analysis, we have demonstrated that ~20% of CC samples exhibit gain of 8q22.3 and 19q13.31; the regions of the genome that encodes the KLF10 and PSG genes, respectively. Gene expression studies demonstrated that there were no alterations in KLF10 mRNA expression, whilst the PSG2 and −5 genes were up- regulated by 1.76 and 3.97-fold respectively in CC compared to normal tissue controls. siRNA and ChIP experiments in SiHa cells have demonstrated that KLF10 participates in immune response through regulation of IL6, IL25 and PSG2 and PSG5 genes. Using cervical tissues from KLF10−/− mice, we have identified down-regulation of PSG17, −21 and −23 and IL11. These results suggest that KLF10 may regulate immune system response genes in cervical cancer among other functions. KLF10 and PSG copy number variations and alterations in mRNA expression levels could represent novel molecular markers in CC.