Downregulation of HOXA1 gene affects small cell lung cancer cell survival and chemoresistance under the regulation of miR-100

Abstract Chemoresistance is often developed in small cell lung cancer (SCLC) patients and leads to poor prognosis. Hox genes, a highly conserved family, play a crucial role in apoptosis, receptor signalling and differentiation. MicroRNAs (miRNAs) have also been shown to play a crucial role in these biological processes by regulating the target genes. Several studies reported that both Hox genes and miRNAs are involved in chemoresistance. The aim of our study is to characterise the clinical significance and functional roles of HOXA1 in SCLC. Expression of HOXA1 was examined in 63 cases of SCLC tissues and 29 cases of blood by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) methods. Multivariate analysis confirmed the prognostic significance of HOXA1 in SCLC patients. Restoration of HOXA1 expression was carried out in SCLC multidrug resistant cell line H69AR and its parental cell line H69 to assess its influence on chemoresistance. Luciferase reporter assay was used to assess HOXA1 as a target of miR-100. The results showed that HOXA1 was expressed in 46% (29/63) of SCLC. Low HOXA1 expression was associated with the poor prognosis of SCLC ( P  P