TARSL2 Emerges as a Key Regulator of Glioblastoma (Gbm) Migration and Invasion

The function of threonyl-tRNA synthetase-like-2 (TARSL2) in glioblastoma (GBM) has gradually attracted attention. Studies have shown that TARSL2 is not only involved in the protein translation process, but may also play important non-classical functions in cancer progression, especially in the migration and invasion of tumor cells.

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Role of TARSL2 in GBM migration and invasion

Promoting Cell Migration

The motility of GBM cells may be influenced by TARSL2 through its control of cytoskeletal remodeling which includes dynamic actin changes. The Rho GTPase signaling pathway interaction by TARSL2 may boost cellular migration capabilities.

Enhancing Tumor Invasiveness

Research demonstrates that TARSL2 can stimulate matrix metalloproteinases (MMPs) expression which breaks down the extracellular matrix (ECM) and boosts tumor cell invasion capabilities. The invasion of GBM cells is promoted through EMT-related gene regulation which reduces E-cadherin levels and increases N-cadherin levels.

Interaction with Signaling Pathways

TARSL2 regulates GBM cell survival, proliferation and invasion by activating signaling pathways including PI3K/AKT/mTOR and Wnt/β-catenin. Integrin expression may become altered which subsequently modifies interactions between cells and between cells and the extracellular matrix.

Fig 1. Structure and physiological role of TARSL2 (Zeng, Q., et al. 2023).

A Direct Functional Target of miR-720 in Glioma

Research has demonstrated that TARSL2 functions as a direct target for miR-720 in glioma and contributes significantly to tumor migration and invasion processes. The study uncovers how the miR-720/TARSL2 axis functions in glioblastoma (GBM) and identifies a new therapeutic target for GBM treatment.

miR-720 Inhibits Expression by Targeting TARSL2

The miRNA binding prediction tools TargetScan, miRDB, and miRanda indicated a potential binding interaction between miR-720 and the 3'UTR of TARSL2. Dual luciferase reporter gene experiments confirmed miR-720's direct interaction with TARSL2 3'UTR which leads to expression inhibition. The expression of TARSL2 mRNA and protein levels decreased in cells with miR-720 overexpression while TARSL2 expression increased when miR-720 activity was blocked as demonstrated by qRT-PCR and Western Blot.

Role of miR-720 in Glioma

Low expression of miR-720: The reduced miR-720 expression found in GBM tissues and cell lines U87 and U251 demonstrates its role as a tumor suppressor miRNA.

High expression of TARSL2: GBM tissues showed elevated TARSL2 expression in conditions where miR-720 expression was reduced which may lead to increased tumor malignancy.

miR-720/TARSL2 Affects GBM Migration and Invasion

Promote Cell Migration

GBM cells lose their migration ability when miR-720 is overexpressed but regain migration function through TARSL2 overexpression. The migration ability of cells might decline due to changes in cytoskeleton remodeling through actin rearrangement.

Inhibit Tumor Invasion

The suppression of TARSL2 by miR-720 limits matrix breakdown through reduced MMP levels such as MMP-2 and MMP-9 which leads to diminished tumor invasiveness. This process targets EMT genes by boosting E-cadherin and suppressing N-cadherin to hinder invasive capabilities.

Affect PI3K/AKT/mTOR Signaling Pathway

TARSL2 activation triggers the PI3K/AKT/mTOR signaling pathway which enhances cell survival and enables migration and invasion. Overexpression of miR-720 reduces GBM cell malignancy by inhibiting TARSL2 and decreasing p-AKT and p-mTOR levels.

TARSL2 as a Potential Therapeutic Target

• Through RNA interference, scientists can suppress TARSL2 expression which results in decreased GBM cell migration and invasion.
• Drug screening identifies small molecule compounds that inhibit TARSL2 function to stop GBM development.
• When TARSL2 inhibitors are used alongside standard treatments such as radiotherapy or chemotherapy they may enhance GBM treatment efficacy.

Increased miR-720 Enhance Glioma Migration and Invasion by Downregulating TARSL2

Research indicates that miR-720 functions as a tumor suppressor in glioma (GBM) by inhibiting glioma movement and penetration through TARSL2 downregulation. The discovery that increased miR-720 enhances GBM migration and invasion indicates miR-720 functions differently in GBM compared to other cancers or its activity varies according to specific cellular environments and signaling pathways.

Possible Mechanism Hypothesis

The following mechanisms may be engaged if miR-720 enhances GBM migration and invasion through TARSL2 downregulation. TARSL2 functions as a tumor suppressor molecule within GBM cells. The downregulation of TARSL2 leads to reduced cytoskeletal stability which makes cells more migratory. The function of TARSL2 in EMT (epithelial-mesenchymal transition) regulation results in GBM cells developing a more invasive mesenchymal phenotype when TARSL2 expression decreases. The downregulation of TARSL2 reduces cell-cell junctions by disrupting cell adhesion molecules including Integrins and increases cell mobility.

miR-720 Activate Other Pro-invasion Pathways

TARSL2 Regulates GBM Invasion and Migration

TARSL2 functions as a key regulator of GBM invasion and migration which offers fresh perspectives on GBM malignant progression mechanisms and suggests a new target for developing future treatment methods. The anti-cancer microRNA miR-720 suppresses GBM cell migration and invasion by targeting TARSL2. The discovery of the miR-720/TARSL2 axis opens new avenues for molecular mechanism research and targeted GBM therapy and holds promise as a future breakthrough in GBM diagnosis and treatment.

References

1. Liu, Y., et al. miR-720 is a key regulator of glioma migration and invasion by controlling TARSL2 expression. Human Cell. 2021, 34: 1504-1516.
2. Zeng, Q., et al. Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development. Journal of Biological Chemistry. 2023, 299.5.