MiR-498 in oesophageal squamous cell carcinoma: clinicopathological impacts and functional interactions

Publication date: Available online 8 February 2017
Source:Human Pathology
Author(s): Farhadul Islam, Vinod Gopalan, Simon Law, Johnny Cheuk-On Tang, Kwok-Wah Chan, Alfred King-Yin Lam
MicroRNA-498 plays a crucial role in progression of many carcinomas. The signalling pathways that miR-498 modulates carcinogenesis are still unknown. Also, miR-498 associated molecular pathogenesis has never been studied in the oesophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in the ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and five ESCC cell lines using quantitative real-time polymerase chain reaction. In vitro effects of miR-498 on cellular process were studied followed by overexpression of miR-498. Western blot and immunofluorescence techniques were used to identify the interacting targets for miR-498 in ESCC. miR-498 expression was significantly reduced in the ESCC when compared to the non-neoplastic oesophageal tissues (P<.05). Patients with low miR-498 expression showed different histological grading of cancer and survival rates when compared to the patients with high miR-498 expression. Overexpression of miR-498 in ESCC cell lines induced remarkable reduction of cell proliferation, barrier penetration and colony formation when compared to control and wild type counterparts. Also, miR-498 activated the FOXO1/KLF6 transcriptional axis in ESCC. In addition, miR-498 overexpression increased p21 protein expression and led to reduced cancer cell growth. To conclude, reduced expression of miR-498 in ESCC as well as in-vitro analysis have confirmed the tumour suppressor properties of miR-498 by modulating the FOXO1/KLF6 signaling pathway. The changes in miR-498 expression may have impacts on the clinical pathological parameters of ESCC as well as in the management of the patients with ESCC.



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