Mansi Bhardwaj1, Seema Sen1, Kunzang Chosdol2, Anjana Sharma3, Neelam Pushker4, Seema Kashyap1, Sameer Bakhshi5, Mandeep S Bajaj4. 1. Department of Ocular Pathology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. 2. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. 3. Department of Ocular Microbiology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. 4. Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. 5. Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
Abstract
BACKGROUND: MicroRNA (miRNA)-200c and miRNA-141 are tumour suppressors, which regulate epithelial-mesenchymal transition (EMT), leading to tumour invasion and metastasis in various malignancies. miRNA-200c and miRNA-141 maintain the epithelial phenotype by post-transcriptionally inhibiting the E-cadherin repressors, zinc finger E-box binding homeobox (ZEB)1 and ZEB2. The present study was performed to determine the prognostic significance of miRNA-200c and miRNA-141, and their association with EMT markers ZEB1, ZEB2 and E-cadherin in eyelid sebaceous gland carcinoma (SGC). METHODS: Expression levels of miRNA-200c and miRNA-141 were determined in 42 eyelid SGC cases by quantitative real-time PCR (qPCR). Their association with ZEB1, ZEB2 and E-cadherin was determined by qPCR and immunohistochemistry. Kaplan-Meier plots and Spearman's rank correlation tests were applied to analyse the data. Patients were followed up for 7-44 months. RESULTS: Low expression levels of miRNA-200c and miRNA-141 were seen in 36/42 (86%) and 28/42 (67%) cases, respectively. Low miRNA-200c correlated significantly with large tumour size (p=0.03) and poor differentiation (p=0.03). Low miRNA-141 correlated significantly with large tumour size (p=0.02) and lymph node metastasis (p=0.04). Survival analysis revealed that patients with low miRNA-200c (p<0.05) and miRNA-141 expression (p=0.07) had shorter disease-free survival. There was a significant association of both miRNA-200c and miRNA-141 with E-cadherin and ZEB2 expression. CONCLUSIONS: Low levels of miRNA-200c and miRNA-141 in patients with eyelid SGC facilitates tumour progression by promoting EMT and miRNA-200c has emerged as a novel potential predictor of survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
BACKGROUND: MicroRNA (miRNA)-200c and miRNA-141 are tumour suppressors, which regulate epithelial-mesenchymal transition (EMT), leading to tumour invasion and metastasis in various malignancies. miRNA-200c and miRNA-141 maintain the epithelial phenotype by post-transcriptionally inhibiting the E-cadherin repressors, zinc finger E-box binding homeobox (ZEB)1 and ZEB2. The present study was performed to determine the prognostic significance of miRNA-200c and miRNA-141, and their association with EMT markers ZEB1, ZEB2 and E-cadherin in eyelid sebaceous gland carcinoma (SGC). METHODS: Expression levels of miRNA-200c and miRNA-141 were determined in 42 eyelid SGC cases by quantitative real-time PCR (qPCR). Their association with ZEB1, ZEB2 and E-cadherin was determined by qPCR and immunohistochemistry. Kaplan-Meier plots and Spearman's rank correlation tests were applied to analyse the data. Patients were followed up for 7-44 months. RESULTS: Low expression levels of miRNA-200c and miRNA-141 were seen in 36/42 (86%) and 28/42 (67%) cases, respectively. Low miRNA-200c correlated significantly with large tumour size (p=0.03) and poor differentiation (p=0.03). Low miRNA-141 correlated significantly with large tumour size (p=0.02) and lymph node metastasis (p=0.04). Survival analysis revealed that patients with low miRNA-200c (p<0.05) and miRNA-141 expression (p=0.07) had shorter disease-free survival. There was a significant association of both miRNA-200c and miRNA-141 with E-cadherin and ZEB2 expression. CONCLUSIONS: Low levels of miRNA-200c and miRNA-141 in patients with eyelid SGC facilitates tumour progression by promoting EMT and miRNA-200c has emerged as a novel potential predictor of survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Ronald O B de Keizer; Anne L M Vriends; Gijsbert J Hötte; Dion A Paridaens; Erik A C Wiemer; Robert M Verdijk Journal: Int J Mol Sci Date: 2022-04-28 Impact factor: 6.208