The carcinogenic advantage generated by miR-21 in NSCLC resides in the target genes involved in multiple pathways such as cell growth and proliferation, angiogenesis, invasion and metastasis, but also chemo- and radioresistance.
More importantly, α-SMA and miR-21 are independent predictors of recurrence and metastasis, with their predictive value of recurrence better than histologic grading.
The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or -amplified [HER2(+)] and inflammatory breast cancer [IBC]).
In particular, miR-21, an oncogenic miRNA is a major player involved in tumor initiation, progression, invasion and metastasis in several cancers, including triple negative breast cancer (TNBC).
We demonstrated that Sphk2 gene silencing induced by nanoparticles in hepatocellular carcinoma (HCC) cells could reduce miRNA-21 sorting into exosomes, contributing to the inhibition of tumor cell migration and tumorigenic function of exosomes to normal liver cells.
Although the reasons for the high relapse are not fully understood, the presence of chemo- and radiotherapy-resistant cancer stem/stem-like cells, where many oncomirs like microRNA-21 (miR-21) are upregulated, could be one of the underlying causes. miR-21 regulates the processes of invasion and metastasis by downregulating multiple tumor/metastatic suppressor genes including PTEN (phosphatase and tensin homolog).
miR-21 was highly expressed in tumour cells of 44% of cases and in cancer stroma of 51% of cases. miR-21 of tumour cells was not related to clinicopathological factors, whereas stromal miR-21 was related to many factors including tumour stage, size, and nodal metastasis.
Because miR-21 appears to be overexpressed in human melanoma, we examined the role of miR-21 in cancer development and metastasis in B16 mouse melanoma cells.
We aimed to evaluate the differential expression of miR-23b and miR-190 which are involved in tumor dormancy, miR-21 involved in metastasis and miR-200b and miR-200c involved in epithelial-mesenchymal transition (EMT) and metastasis, in the plasma of patients with early and metastatic breast cancer (MBC).
Cell models with bioinformatics approaches may help distinguish functional genes. miR‑652-5p, miR‑21‑5p, and their potential target genes may participate in ESCC development and metastasis.
Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAKT levels in these two lines.
Studies on glioma, colon cancer cells, hepatocellular cancer cells and breast cancer cells have indicated that miR-21 is involved in tumor growth, invasion and metastasis.
Furthermore, Transwell assay results revealed that downregulation of HBx and treatment with miR‑21 inhibitors contributed to the inhibition of MHCC‑97H cell invasion and metastasis.
High serum miR-21 was significantly correlated with tumor-node metastases stage and lymph node metastasis of NSCLC patients (P = 0.016 and 0.026, respectively).
Exosome biomarkers (such as HER2, CD47, Del-1, miR-1246 and miR-21) in breast cancer patients are significantly higher than those in healthy controls, exosomal GSTP1 and TRPC5 are related to chemotherapy resistance, exosome-carrying TRPC5, NANOG, NEUROD1, HTR7, KISS1R and HOXC are correlated to PFS, DFS or OS, and some exosomal proteins (HER2, KDR, CD49d, CXCR4 and CD44) as well as miRNAs (miR-340-5p, miR-17-5p, miR-130a-3p, miR-93-5p) are associated with tumor recurrence or distant organ metastasis.