The Therapeutic Potential of PTEN Modulation: Targeting Strategies from Gene to Protein

Abstract

Two decades have passed since the discovery of the tumor suppressor, PTEN. A multitude of biological functions have since been revealed, suggesting potential therapeutic applications for both PTEN activation (e.g., cancer) and inhibition (e.g., neuroregeneration). Nevertheless, PTEN's therapeutic suitability has been called into question due to its "risky" profile as a tumor suppressor. To evaluate PTEN function and its various roles in disease a number of molecules have so far been developed. However, intrinsic problems associated with phosphatase inhibition and PTEN's complex regulation via post-translational modifications hinder straightforward access to selective modulators. For this reason, central questions associated with PTEN targeting remain unanswered. In this perspective, we summarize current PTEN-targeting strategies and discuss potential approaches to modulate its functional dose, considering all stages of PTEN biogenesis from direct protein modulation to the targeting of relevant miRNAs as well as the PTEN gene and mRNA.

Activation of the oncogenic miR‐21‐5p promotes HCV replication and steatosis induced by the viral core 3a protein

“…Regarding PTEN, therapeutic approaches aiming at restoring its activity to physiological levels are also pertinent. However, the multitude and high complexity of mechanisms (epigenetic, transcriptional, post‐transcriptional and post‐translational) regulating PTEN expression and activity have to date hindered the discovery of clinically relevant and selective PTEN modulators …”

MiR‐205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression

“…PTEN is a tumour suppressor of human cancer and has critical roles in the regulation of tumorigenesis and cell migration. Studies have shown that PTEN plays a crucial role in regulating the PI3K/Akt signalling pathway and that activation of Akt inhibits the autophagy pathway . Furthermore, PTEN has been reported to play a major role in inhibiting migration and invasion of tumour cell via the Akt/SP1/MMP2 pathway .…”

“…40 To detect whether miR-205 influences EPC migration by regulating F-actin filaments and MMP2, we performed way. 48,49 Furthermore, PTEN has been reported to play a major role in inhibiting migration and invasion of tumour cell via the Akt/SP1/ MMP2 pathway. 50 Intriguingly, autophagy inhibition promoted EPC migration by up-regulating MMP2 expression.…”

RNA Structure and Cellular Applications of Fluorescent Light‐Up Aptamers

“…[1][2][3][4] RNAs are in constant dynamic interaction with other biomolecules such as proteins [5][6][7][8][9][10][11] and other RNAs (e.g.,s nRNAs,l ncRNAs, miRNAs), [12][13][14] thereby significantly altering cellular function and cell fate. [1][2][3][4] RNAs are in constant dynamic interaction with other biomolecules such as proteins [5][6][7][8][9][10][11] and other RNAs (e.g.,s nRNAs,l ncRNAs, miRNAs), [12][13][14] thereby significantly altering cellular function and cell fate.…”

“…RNAh as been recognized as am ajor player in cellular function for decades now; however,r obust methods to directly measure and understand the different functions of RNAi nc ells are still under development. [1][2][3][4] RNAs are in constant dynamic interaction with other biomolecules such as proteins [5][6][7][8][9][10][11] and other RNAs (e.g.,s nRNAs,l ncRNAs, miRNAs), [12][13][14] thereby significantly altering cellular function and cell fate. [15][16][17][18] State-of-the-art methods to detect an RNA of interest (ROI) and its cellular interactions include fluorescence in situ hybridization (FISH) [19,20] and the MS2-green fluorescent protein (MS2-GFP) system where the interaction between an RNAd erived from enterobacteria phage MS2 and the MS2 coat protein fused to GFP is used to detect an ROI.…”