Although some studies have shown that increased miR-146a levels are associated with HCC, others have revealed that miR-146a suppresses cancer cell proliferation, invasion and metastasis.
There is a close link between high miR-146a-5p expression and better overall survival in 21 types of solid cancer, especially in reproductive system and digestive system cancers.
This review goes into an in-depth look at the most recent finding regarding the significance of one particular miRNA, miR-146a-5p, and its involvement in cancer.
Of relevance, overexpression of miR-146a in metastatic clones showed reduced in vitro malignancy and abolished the development of primary tumor and liver metastases.
A negative correlation was demonstrated between miR-146a expression in primary tumors and serum levels of cancer antigen 125 (R=-0.37; P=0.03) and Risk of Malignancy Algorithm index (R=-0.79; P=0.0007).
In this study, we investigated the effects of OPM2 (a MM cell line) exosomes (OPM2-exo) on regulating the proliferation, cancer-associated fibroblast (CAF) transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects.
We further performed functional studies of three microRNA variants associated with cancer (rs2910164:C > G in MIR146A, rs11614913:C > T in MIR196A2, and rs3746444:A > G in both MIR499A and MIR499B).
miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164).
The microRNA miR146a has a potential role in the development of breast cancer and the effects of its SNPs require further inquiry to determine the nature of their influence on breast tissue and cancer.
Our study suggested that urinary miR-146a-5p might be useful as a new noninvasive diagnostic marker, therapeutic target, or anticancer agent for bladder cancer, as well as for increasing our understanding of cancer biology.
However, the molecular details underlying miR-146a mediated regulation of its target genes and its precise biological function in cancer, especially in hepatocellular carcinoma (HCC) remains unclear.
Using a large population-based case-control study of basal cell (BCC) and squamous cell carcinoma (SCC), we investigated the impact of MIR146A SNP rs2910164 on cancer risk, and interaction with a SNP in one of its putative targets (RNASEL, rs486907).
Chi-square test was used to assess the different distribution of miR-146a polymorphism between NPC patients and controls; and logistic regression analysis was applied to analyze the associations between miR-146a polymorphism with cancer risk in different contrast models.
Our current study primarily aimed to confirm previously conducted association studies between rs2910164 found on miR-146a, and rs11614913 located on miR-196a2 polymorphisms and cancer phenotypes in the Japanese elderly population. rs2910164 (G/C) and rs11614913 (T/C) polymorphisms were determined by genotyping on the samples collected from 1,351 consecutive autopsy cases registered in the Japanese SNPs for geriatric research (JG-SNP) data base.
This intriguing hypothesis is supported by several observations: i) in endothelial cells undergoing replicative senescence (HUVECs), a well-established model of cell senescence, miR-146a, miR-34a, and miR-181a are over-expressed whereas their target Bcl-2 is down-regulated; ii) IPA of the miR-146a, miR-34a and miR-181a network shows that they are closely linked to each other, to Bcl-2 and to mitochondria; and iii) miR-146a, miR-34a, and miR-181a are involved in important cell functions (growth, proliferation, death, survival, maintenance) and age-related diseases (cancer, skeletal and muscle disorders, neurological, cardiovascular and metabolic diseases).
A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146ars2910164 and miR-499 rs3746444 are crucial.