PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth.

Molecular Oncology
Neha SinghVirginie Olive

Abstract

The proviral integration site for Moloney murine leukemia virus (PIM) serine/threonine kinases have an oncogenic and prosurvival role in hematological and solid cancers. However, the mechanism by which these kinases drive tumor growth has not been completely elucidated. To determine the genes controlled by these protein kinases, we carried out a microarray analysis in T-cell acute lymphoblastic leukemia (T-ALL) comparing early progenitor (ETP-ALL) cell lines whose growth is driven by PIM kinases to more mature T-ALL cells that have low PIM levels. This analysis demonstrated that the long noncoding RNA (lncRNA) H19 was associated with increased PIM levels in ETP-ALL. Overexpression or knockdown of PIM in these T-ALL cell lines controlled the level of H19 and regulated the methylation of the H19 promoter, suggesting a mechanism by which PIM controls H19 transcription. In these T-ALL cells, the expression of PIM1 induced stem cell gene expression (SOX2, OCT-4, and NANOG) through H19. Identical results were found in prostate cancer (PCa) cell lines where PIM kinases drive cancer growth, and both H19 and stem cell gene levels. Small molecule pan-PIM inhibitors (PIM-i) currently in clinical trials reduced H19 expression in both of th...Continue Reading

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Citations

Nov 23, 2020·Cancer Letters·Yun Wei Shermane LimBoon-Cher Goh
Jul 26, 2021·European Journal of Pharmacology·Chunyuan TangLushan Yu
Aug 30, 2021·Biochimica Et Biophysica Acta. General Subjects·Aanchal RathiMd Imtaiyaz Hassan

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Methods Mentioned

BETA
PCR
Protein Assay
transfection
Assay
flow cytometry
FACS
chip
transfections
xenograft
xenografts

Software Mentioned

ComboSyn
imagej
Affymetrix® transcriptome analysis console
Affymetrix

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