The Relationship Between of Expression Mirna Let-7a-1 and Mirna Let-7f-1 with Expression of Genes IL6, IL8, and Vascular Endothelial Growth Factor A (VEGF A) in Endometrioum Endometriosis Patients

Abstract

Endometriosis is a chronic inflammatory, oestrogen-dependent disease in which local inflammation and angiogenesis, mediated in part by interleukin (IL)-6, IL-8, and vascular endothelial growth factor A (VEGF-A), drive lesion growth, yet the contribution of the let-7 family of microRNAs to this process remains poorly defined. This cross-sectional study evaluated endometrial expression of miRNA let-7a-1 and let-7f-1 in relation to disease severity and to IL-6, IL-8, and VEGF-A expression. Sixty-five women undergoing clinically indicated hysteroscopy, laparoscopy, or operative laparotomy at three hospitals in Makassar and Maros, Indonesia (January–June 2023) were enrolled by consecutive sampling: 32 with histologically confirmed endometriosis (7 mild, 12 moderate, 13 severe, ASRM classification) and 33 disease-free controls. Endometrial tissue miRNA and mRNA levels were quantified by reverse-transcription quantitative PCR. Groups did not differ in education level (p = 0.563) or nutritional status (p = 1.000) but differed in age (p < 0.001). Let-7a-1 expression did not differ significantly across severity categories (p = 0.265) or between cases and controls (p = 0.068). In contrast, let-7f-1 expression differed significantly across severity categories (p = 0.023) and was markedly lower in all endometriosis subgroups than in controls (overall p < 0.001; mild vs control p = 0.018, moderate vs control p < 0.001, severe vs control p < 0.001). Neither miRNA correlated with IL-6, IL-8, or VEGF-A expression within any endometriosis severity subgroup, but in controls let-7f-1 correlated positively with IL-8 (r = 0.478, p = 0.033) and with VEGF-A (r = 0.467, p = 0.050). These findings indicate that let-7f-1, rather than let-7a-1, is consistently downregulated in endometriotic endometrium and warrants further evaluation as a candidate biomarker, while its coupling to inflammatory–angiogenic signalling appears to be disrupted specifically in disease tissue.