Clinico-Pathological Importance of miR-146a in Lung Cancer

Abstract

Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health in the 21st century. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20–25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz. TNF-α, NF-κB and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.

A comprehensive cancer-associated microRNA expression profiling and proteomic analysis of human umbilical cord mesenchymal stem cell derived exosomes.

“…Additionally, the varied expression of miRNAs indicates their involvement in a variety of activities in the target cells. Studies have reported that the miR146 was downregulated in various cancers, including non-small cell lung cancer (NSCLC), and its upregulation inhibits cellular proliferation by directly degrading the EGFR mRNA [59][60]. Similarly, miR-215 acts as a tumor suppressor by blocking the EGFR ligand epiregulin, and its transcriptional regulator HOXB9 [61], which was upregulated in hUCMSC derived exosomes, con rming their tumor suppressor activity.…”

Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands

“…Furthermore, high miR-146a expression showed longer progression-free survival in tissues of NSCLC patients. As a result, miR-146a is a potent prognostic biomarker in NSCLC [85][86][87]. Moreover, the expression levels of miR-128b were lower in NSCLC carcinoma tissues than in adjacent non-neoplastic tissues, whereas the expression of EGFR mRNA was the opposite.…”

“…Interestingly, these effects were independent of the EGFR mutation status (wild type, resistance mutation, or sensitizing mutation). Hence, miR-146a is a strong prognostic biomarker and therapeutic candidate in NSCLC [85][86][87]. qRT-PCR assay unveiled higher miR-214 expression in the acquired erlotinib-resistant HCC827 (HCC827/ER) cells than in HCC827 cells and in NSCLC patients' plasma with acquired EGFR-TKI resistance compared to those before exposure to EGFR-TKI therapy.…”

“…MiR-146a also suppressed these NSCLC cells' migration. These miR-146a-dependent effects are due to its targeting of NF-κB and EGFR signalings [85][86][87][140][141][142]. Cytokines (e.g., IFN-gamma and IL-6) bind to their respective cytokine receptors (CRs), leading to its activation.…”

Sensitivity of Plasma Micrornas as a Probable Non-Small Cell Lung Cancer Biomarker and Its Significance

“…Blood plasma is obviously the best option for developing these diagnostic markers. Many molecular alterations of specific tumors are recognized in serum or plasma and have been revealed to be a biomarker in lung cancer patients [6][7] . However, none of the markers tested so far has achieved the features allowing for the NSCLC diagnosis.…”