MicroRNAs expression analysis shows key affirmation of Synaptopodin-2 as a novel prognostic and therapeutic biomarker for colorectal and cervical cancers

Abstract

MicroRNAs play a crucial role in tumorigenesis, tumor progression, and metastasis, and thus they contribute in development of different malignancies including cervical cancer (CC) and colorectal cancer (CRC). Through integrated strategies of computational biology, this study aims to identify prognostic biomarkers responsible for CRC and CC prognosis, and potential therapeutic agents to halt the progression of these cancers. Expression analysis of miRNA datasets of CRC and CC identified 17 differentially expressed miRNAs (DEMs). SYNPO2, NEGR1, FGF7, LIFR, RUNX1T1, CFL2, BNC2, EPHB2, PMAIP1, and CDC25A differentially expressed genes (DEGs) regulated by these DEMs were classified as candidate genes responsible for CRC and CC. Down-regulation of Synaptopodin-2 (SYNPO2) is involved in emergence and progression of these cancers by activating ER, PI3K/AKT, and EMT pathways as well as by suppressing DNA damage response, and cell cycle pathways. Higher methylation rate in promoter region of SYNPO2 could be a possible reason for lowering the expression of SYNPO2 in tumor stages. Hence, the lower expression of SYNPO2 is associated with poor prognosis of CRC and CC and could function as prognostic biomarker and therapeutic target. Fourteen transcription factors were recognized which can activate/inhibit the transcription of SYNPO2 and may be a potential target to regulate expression of SYNPO2 in CRC and CC. Retinoic acid and Estradiol were identified as putative therapeutic drugs for CRC and CC patients. This study will thus help in understanding the underlying molecular events in CRC and CC that may improve the detection of malignant lesions in primary screening and will broaden the clinical applications.