These findings present a novel regulatory mechanism of 15-PGDH by miR-21, and how dysregulated expression of miR-21 may contribute to loss of 15-PGDH expression and promote CRC progression via increased accumulation of PGE<sub>2</sub>.
In this review, we summarize the potential diagnostic, prognostic, and therapeutic values of miR-21 in CRC progression for a better understanding and hence a better management of this disease.
A case-control study including 1147 patients and 1203 controls was performed to evaluate the association of SNPs in miR-21 binding sites and colorectal cancer risk.
Moreover, the analysis of ROC curves revealed that AUC (95% CI) of miR-182, miR-183, miR-141, and miR-21 in diagnosis of CRC was 0.76 (0.66-0.87), 0.85 (0.78-0.94), 0.77 (0.62-0.92), 0.83 (0.73-0.90), respectively.
Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value.
Mounting evidence suggests that many miRNAs are overexpressed (miR-21, miR-329, miR-181a, miR-199a, miR-382 and miR-215) in CRC CAFs, and these miRNAs can influence the spread, invasiveness and chemoresistance in neighboring tumor cells via paracrine signaling.
Mechanistically, miR-21-5p and miR-155-5p were transferred to colorectal cancer cells by MDE and bound to the BRG1 coding sequence, downregulating expression of BRG1, which has been identified as a key factor promoting the colorectal cancer metastasis, yet is downregulated in metastatic colorectal cancer cells.
Our findings support the important role of miR-21 in stages I-II of CRC, and the KRAS G12D mutant, and differential miR-148a expression, in advanced stages of CRC.
The expression level of miR-21 in the serum of CRC patients was significantly higher compared with healthy people, while the expression of miR-145 in the serum of CRC patients was significantly lower than that in healthy people.
<i>TP53, KRAS, APC</i>) has limited diagnostic sensitivity (40-60%), however, methylated DNA including <i>SEPT9, SFRP1, SDC2</i> can be applied with higher sensitivity (up to 90%) for CRC.Circulating miRNAs (e.g. miR-21, miR-92, miR-141) provide comparably high sensitivity for CRC as the circulating tumor cell mRNA markers (e.g.EGFR, CK19, CK20, CEA).
The most important mechanisms of Fusobacterium nucleatum involved in CRC carcinogenesis are immune modulation (such as increasing myeloid-derived suppressor cells and inhibitory receptors of natural killer cells), virulence factors (such as FadA and Fap2), microRNAs (such as miR-21), and bacteria metabolism.
A 5-serum miRNA panel (miRNA-1246, miRNA-202-3p, miRNA-21-3p, miRNA-1229-3p, and miRNA-532-3p) effectively distinguished CRCs from HCs with 91.6% sensitivity and 91.7% specificity.
Finally, <i>KRAS</i> mutations were more frequently observed in CRC samples infected with <i>F. nucleatum</i> and were associated with greater expression of miR-21 in CRA, while <i>IL8</i> was upregulated in MSI-high CRC.
Our studies suggest that the regulation of HDAC, hTERT and miR-21 is a promising approach for delaying and/or preventing CRC and may be accomplished via the consumption of SFN in cruciferous vegetables.
This meta-analysis reports significant prognostic value of miR-21 in predicting worse overall survival (OS) in ESCC, PDAC, and CRC with pooled hazard ratio (HR) of 3.49 (95% CI 2.58-4.71, p-value < 0.01).
We found that ASOs could effectively inhibit the growth and metastasis of CRC in vivo, accompanied by downregulated expression of miR-21 and reduced transduction of the AKT and ERK pathway.