MicroRNA-434-3p regulates age-related apoptosis through eIF5A1 in the skeletal muscle

Patricia S. Pardo, Ameena Hajira, Aladin M. Boriek, Junaith Mohamed

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Increased activation of catabolic pathways, including apoptosis causes sarcopenia. However, the precise molecular mechanism that initiates apoptosis during aging is not well understood. Here, we report that aging alters miRNA expression profile in mouse skeletal muscle as evidenced by miRNA microarray and real-time PCR. We identified miR-434-3p as a highly downregulated miRNA in the skeletal muscle of aging mice. Myocytes transfected with miR-434-3p mimic prevents apoptosis induced by various apoptotic stimuli, and cotransfection of miR-434-3p antagomir abolishes the inhibitory role of miR-434-3p. We found that miR-434-3p inhibits apoptosis by targeting the eukaryotic translation initiation factor 5A1 (eIF5A1). Overexpression of miR- 434-3p in myocytes reduces the loss of mitochondrial transmembrane potential, and activation of caspases-3, - 8 and -9 by suppressing eIF5A1 in response to various apoptotic stimuli whereas inhibition of miR-434-3p reversed this scenario. Skeletal muscles from aging mice exhibit low levels of miR-434-3p and high levels of eIF5A1, suggesting a possible role for miR-434-3p in the initiation of apoptosis in aging muscle. Overall, our data identified for the first time that miR-434-3p is an anti-apoptotic miRNA that may be therapeutically useful for treating muscle atrophy in various pathophysiological conditions, including sarcopenia.

Original languageEnglish (US)
Pages (from-to)1012-1029
Number of pages18
JournalAging
Volume9
Issue number3
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

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Eukaryotic Initiation Factors
MicroRNAs
Skeletal Muscle
Apoptosis
Sarcopenia
Muscle Cells
Muscular Atrophy
Caspase 8
Caspase 3
Membrane Potentials
Real-Time Polymerase Chain Reaction
Down-Regulation
Muscles

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

Cite this

MicroRNA-434-3p regulates age-related apoptosis through eIF5A1 in the skeletal muscle. / Pardo, Patricia S.; Hajira, Ameena; Boriek, Aladin M.; Mohamed, Junaith.

In: Aging, Vol. 9, No. 3, 01.01.2017, p. 1012-1029.

Research output: Contribution to journalArticle

Pardo, Patricia S. ; Hajira, Ameena ; Boriek, Aladin M. ; Mohamed, Junaith. / MicroRNA-434-3p regulates age-related apoptosis through eIF5A1 in the skeletal muscle. In: Aging. 2017 ; Vol. 9, No. 3. pp. 1012-1029.
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