A novel tonicity-responsive microRNA miR-23a-5p modulates renal cell survival under osmotic stress through targeting heat shock protein 70 HSPA1B.

American Journal of Physiology. Cell Physiology
Kang KangDeming Gou

Abstract

There is growing evidence that microRNAs (miRNAs) are implicated in cellular adaptation to osmotic stress, but the underlying osmosignaling pathways are still not completely understood. In this study, we found that a passenger strand miRNA, miR-23a-5p, was significantly downregulated in response to high NaCl treatment in mouse inner medullary collecting duct cells (mIMCD3) through an miRNA profiling assay. The decrease of miR-23a-5p is hypertonicity-dependent and osmotolerant cell type-specific. Knockdown of miR-23a-5p increased cellular survival and proliferation in mIMCD3. In contrast, miR-23a-5p overexpression repressed cell viability and proliferation under hypertonic stress. RNA deep-sequencing revealed that a heat shock protein 70 (HSP70) isoform, HSP70 member 1B (HSPA1B), was significantly increased under hypertonic treatment. Based on the prediction analysis by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and TargetScan, and a further validation via a dual-luciferase assay, HSPA1B was identified as a potential target of miR-23a-5p. Overexpressed miR-23a-5p suppressed HSPA1B, whereas downregulated miR-23a-5p promoted HSPA1B expression in mIMCD3. In addition, an in vivo study demonstrated that there...Continue Reading

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Citations

Jun 11, 2021·Wiley Interdisciplinary Reviews. RNA·Subhashis NatuaSanjeev Shukla

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Methods Mentioned

BETA
transfection
Protein Assay
PCR
environmental osmotic stress
RNA-Seq

Key Resources (RRID) Mentioned

AB_2210695

Software Mentioned

Targetscan
GraphPad
Cuffdiff
Expdiff
KOBAS
Short Oligonucleotide Analysis Package ( SOAP )
GraphPad Prism
HISAT2

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