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. Author manuscript; available in PMC: 2021 Jul 14.
Published in final edited form as: Cond Med. 2017 Dec 15;1(1):35–46.

Figure 1: miR-21 regulates apoptosis.

Figure 1:

Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN) are the best-characterized targets of miR-21. These proteins synergistically promote apoptosis. FasL is either membrane-bound or soluble and physically binds to the Fas death receptor (FasR) to initiate a caspase cleavage cascade resulting in apoptosis. PTEN is a tumor suppressor and a negative regulator of PI3K that phosphorylates PIP2 to form PIP3 that activates Akt pathway leading to cell death. As such, prevention of PTEN by miR-21 can lead to better cell survival following conditions like stroke and TBI. PI3K and Akt also modulate caspase-9 cleavage and hence, PTEN inhibition leads to prevention of apoptosis. Furthermore, PI3K/Akt activates mammalian target of rapamycin (mTOR) that inhibits PDCD4 activity. PDCD4 causes a protein expression bottleneck by inhibiting eukaryotic initiation factor 4a (eIF4a) and the transcription factor activator protein 1 (AP-1). Preventing eIF4a activity causes endoplasmic reticulum stress and inhibiting AP-1 prevents expression of beneficial genes such as vascular endothelial growth factor (VEGF). As inhibition of FasL, PTEN or PDCD4 together is a powerful strategy to prevent apoptosis and hence miR-21 is an attractive therapeutic to protect the post-injury brain. Tipped arrows indicate activation and blunted arrows indicate inhibition.