Aim: Despite the reports in many cancers including gastrointestinal cancers, the functional roles of miR-498 have not been studied in oesophageal squamous cell carcinoma (ESCC). This study aimed to examine the functional characteristics of miR-498 and to identify the interacting targets of miR-498 in ESCC.
Methodology: Expression levels of miR-498 was investigated in ESCC cell lines (KYSE-70 and KYSE-520), and a normal squamous epithelial cell line (HACAT) using quantitative real-time polymerase chain reaction (qRT-PCR). In vitro effects of miR-498 on cellular process such as proliferation, invasion and migration and colony formation were studied followed by the exogenous overexpression of miR-498. Western blot and immunofluorescence techniques were used to analyse the expression levels of the miR-498 targeted proteins in ESCC cell lines.
Results: Expression levels of miR-498 was significantly (p<0.01) reduced in ESCC cells when compared to the non-neoplastic cells. miR-498 overexpression in ESCC cells (KYSE-70+miR-498 and KYSE-520+miR-498 ) induced remarkable reduction of cancer cell proliferation, invasion and colony formation (p<0.01) when compared to control (KYSE-70/KYSE-520miRScr) and wildtype (KYSE-70/KYSE-520wildtype) counterparts. Also, miR-498 activated the FOXO1/KLF6 axis of transcriptional networks as well as p21 protein expression, which in turn caused the miR-498 guided reduction in ESCC cell growth and proliferation.
Conclusion: Upregulation of miR-498 expression in ESCC induced tumour inhibitory features of ESCC cell in vitro via modulating FOXO1/KLF6 signaling pathway and repressing oncogenic properties of cells. Therefore, miR-498 play a key role in the pathogenesis of ESCCs and its modulation may have potential therapeutic implications in the management of patients with ESCC.