An assessment of the relationship between the expression of CCR7/CCL19 axis and selected regulatory miRNAs in non-small cell lung cancer

Abstract

CC chemokine receptor type 7 (CCR7) and its ligands has been implicated in the occurrence and progression of NSCLC. Previous studies have revealed that the diagnostic value of CCR7/CCL19 axis in lung tumorigenesis remains controversial. The present study evaluates the relationship between the mRNA expression of CCR7/CCL19 axis and selected regulatory miRNAs in NSCLC patients. It analyzes the expression level of CCR7 mRNA and its ligand in tumor tissue in relation to expression level of two miRNAs: miR let-7a and miR-335, as transcriptional regulators of study genes. Twenty-seven patients (n = 27) were enrolled. The expression of the studied genes and miRNAs was evaluated by qPCR. Tumour tissue fragments, adjacent macroscopically-unchanged lung tissue (control) and patient serum were used as biological material for study. Elevated expression of CCR7 and CCL19 mRNA was observed in patients with metastasis to lymph nodes. We noticed upregulated miR-335 expression and downregulated miR let-7a expression in patient serum with regard to AJCC tumor staging. Higher miR-335 expression and lower miR let-7a expression level was observed in patients with metastasis to lymph node. The presence of changes observed in the expression level of miR-335 and miR let-7a in the serum of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression; however, this observation requires further investigation.

The Significance of the Alter miR let-7a and miR-335 Expression Level Regulating the CCR7/CCL19 Axis as Potential Biomarkers of Tumor Progression in NSCLC

“…This research is a continuation and extension of our earlier study, the aim of which was to evaluate changes in the expression level of CCR7 and CCL19 in tumor tissue and of two regulatory miRNAs of these genes (miR let-7a and miR-335) in serum exosomes [16]. A particularly valuable element of this study is the measurement of miRNA expression level in tumor tissue.…”

“…The biological material was secured and prepared according to the protocol described in the previous article [16]. Isolation of total RNA from tissue and exosomes was performed with the same type of isolation kits as before.…”

Exploring Specific miRNA-mRNA Axes With Relationship to Taxanes-Resistance in Breast Cancer

“…In NSCLC, a study observed an upregulation of CXCL9/CCR7 in tumor tissue, especially in patients with metastasis to lymph nodes. Intriguingly, the expression of CXCL9/CCR7 were associated with two miRNAs: let-7a and miR-335 (57). In addition, high expression of CXCL9 was observed in melanoma-derived cancer stem cells (CSC), which may accelerate efficient recognition and kill by NK cells (58).…”

CCL19 has potential to be a prognostic biomarker and a modulator of tumor immune microenvironment (TIME) of breast cancer: a comprehensive analysis based on TCGA database

“…Further analysis between the expression of CCL19 and the survival of patients or TICs in TIME suggested that CCL19 was not only signi cantly associated with the survival and clinicpathological characteristics of BC patients, but also participated in the regulation of TIME partly through closely communicating with multiple TICs, including macrophages, T cells, B cells, NK cells, DCs, mast cells and neutrophils. Previous studies indicated that CCL19 greatly participated in cancer cell proliferation, angiogenesis, migration, invasion and immune cell in ltration [23] in multiple cancers, including gastric cancer [29] , colorectal cancer [30] , non-small cell lung cancer [31,32] , lymphoma [33] and melanoma [13] . These biological functions of CCL19 were involved in the activation of CCR7/absent in melanoma 2 (AIM2) signaling pathway [29] , interaction with miRNAs [30] , the migration and maturation of DC [34] and migration of NK cells [35] .…”