Target intelligence / Profile preview

Maternal embryonic leucine zipper kinase (MELK) mRNA (MELK mRNA)

Target
MELK mRNA
Molecular classification
Messenger RNA, Other
01

Overview

Maternal embryonic leucine zipper kinase (MELK) mRNA is the transcript of the MELK gene, which encodes a serine/threonine kinase involved in cell cycle regulation and stem cell maintenance. This mRNA is significantly overexpressed in various aggressive cancers, such as triple-negative breast cancer (TNBC) and glioblastoma multiforme (GBM), while remaining nearly undetectable in most normal adult tissues. High levels of MELK mRNA are strongly associated with poor prognosis, tumor recurrence, and resistance to radiation and chemotherapy. As a therapeutic target, MELK mRNA can be directly addressed using RNA interference (RNAi) or antisense oligonucleotides (ASOs) to prevent the translation of the oncogenic protein. Additionally, small molecule inhibitors like OTS167 target the resulting protein's kinase activity, effectively disrupting the signaling pathways that promote cancer cell survival and proliferation. Recent research also highlights the role of MELK as a host factor in viral infections, suggesting that targeting its expression could have broad therapeutic applications. However, the essentiality of MELK for tumor growth has been debated following CRISPR/Cas9 studies, which suggests that some observed anti-tumor effects may be due to off-target activity.

Other names
Maternal embryonic leucine zipper kinase transcriptMELK transcriptHPK38 mRNAMPK38 mRNApEg3 mRNA
02

Mechanism of action

Direct degradation of the mRNA transcript via RNA interference (siRNA) to prevent protein translation, or competitive inhibition of the encoded kinase's ATP-binding pocket by small molecules to disrupt downstream signaling.

03

Biological functions

Cell cycle regulationCell proliferationApoptosis regulationStem cell maintenanceSpliceosome assemblyProtein synthesis template
04

Disease associations

CancerTriple-negative breast cancerGlioblastomaLung cancerNeuroblastomaColorectal cancerAcute myeloid leukemiaInfluenza
05

Safety considerations

Off-target effects of RNA-targeting modalitiesPotential toxicity in normal proliferative tissues (e.g., testis, embryonic cells)Controversy regarding the essentiality of MELK for tumor growth as suggested by CRISPR/Cas9 studies
06

Interacting drugs

OTS167 (OTSSP167)

2 more in the full profile.

07

Biomarkers

MELK mRNA expression levelMELK protein levelKi67 expressionFOXM1 phosphorylationDEPDC1 expression

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