PP2A was a direct target of miR-21, which participated in the effects of ASBEL and miR-21 on the activation of phosphatidylinositol 3-kinase/protein kinase 3/glycogen synthase kinase-3β (PI3K/AKT/GSK3β) and mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion.
Upon comparison of clinicopathological factors, miR-21 expression showed significant association with depth of invasion, lymphatic and venous invasion, liver metastasis and Dukes' stage.
Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164).
It has been reported that miR-21 is upregulated in hepatocellular carcinoma (HCC), and overexpressed miR-21 plays a key role in promoting cell cycle progression, reducing cell death and favoring angiogenesis and invasion.
Furthermore, PTEN and p-AKT were shown to participate in the regulation of miR-21-5p on EMT phenotypes and stemness signatures of keloid keratinocytes, which might account for the invasion and recurrence of keloids.
Meanwhile, lentiviral vector-mediated overexpression of miR-21 not only conferred resistance to 5-FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC-1 cells.
Downregulation of miR-21 by miR-21 inhibitor increases RECK expression and decreases cell invasion, suggesting that downregulation of miR-21 by solasodine may contribute to elevate RECK expression and subsequently inhibiting cell invasion.
High expression of miR-21 and low expression of miR-145 are closely related to the development and progression of CRC, especially with the grade of differentiation, invasion, metastasis and clinical stage.
Using the SK-NEP-1 WT cell line, we showed that the decreased expression levels of miR-21 promoted cell proliferation and invasion, but inhibited apoptosis.
Modulation of miR-21 altered focal adhesion kinase phosphorylation and expression of matrix metalloproteases 2 and 9, both downstream mediators of PTEN involved in cell migration and invasion.
Silencing of HIF-1α or NF-κB decreased colony formation and the invasion and migration capacities of CSE-transformed HBE cells; however, up-regulation of miR-21 reversed these effects.
Patients with advanced Tumor-Node-Metastasis (TNM) stage, lymph node metastasis, local invasion and higher serum carcinoembryonic antigen (CEA) levels displayed significantly high expression of miR-21.
Invasion assays and western blot analyses revealed that the overexpression of miRNA-21 significantly enhanced the invasion ability of MG-63 cells and the expression of phosphorylated (p-)AKT, while downregulation of miRNA-21 expression reduced the protein level of AKT and p-AKT.
Targeting of microRNA-21 is sufficient to limit tumor cell proliferation and invasion in a manner that is likely to involve associated changes in multiple targets, suggesting that suppression of microRNA-21 may be a novel approach for the treatment of hepatocellular carcinoma.
Finally, western blotting was performed to determine if miR-21 regulated expression of signal transducers and activators of transcription 3 (STAT3), and assays of cell proliferation, colony formation, migration and invasion were performed to examine the role of STAT3 in regulation of breast cancer cells.
The study shows there are high expressions of miR-21 in tongue squamous cell carcinoma cell lines (Tca8113 and its high metastatic lines), especially in high metastatic lines. miR-21 silencing could suppress the capacity of proliferation, migration and invasion, arrest the cell cycle and induce apoptosis of tongue squamous cell carcinoma cell lines (Tca8113 and its high metastatic lines).
In conclusion, microRNA-21 is crucial for CCA carcinogenesis and metastasis, which could induce EMT process, thereby promote the invasion and migration of CCA cells.
The present study showed the upregulation of miR-21 in invasive cervical cancers, and confirmed the promotion of miR-21 with regard to the proliferation, migration and invasion in cervical cancer cells via inhibiting the PTEN expression.