MiR-185 targets POT1 to induce telomere dysfunction and cellular senescence.

Aging
Tingting LiYan Huang

Abstract

Protection of telomere 1 (POT1), the telomeric single-stranded DNA (ssDNA)-binding protein in the shelterin complex, has been implicated in the DNA damage response, tumorigenesis and aging. Telomere dysfunction induced by telomere deprotection could accelerate cellular senescence in primary human cells. While previous work demonstrated the biological mechanism of POT1 in aging and cancer, how POT1 is posttranscriptionally regulated remains largely unknown. To better understand the POT1 regulatory axis, we performed bioinformatic prediction, and selected candidates were further confirmed by dual-luciferase reporter assay. Collectively, our results revealed that miR-185 can significantly reduce POT1 mRNA and protein levels by directly targeting the POT1 3'-untranslated region (3'-UTR). Overexpression of miR-185 increased telomere dysfunction-induced foci (TIF) signals in both cancer cells and primary human fibroblasts. Elevated miR-185 led to telomere elongation in the telomerase-positive cell line HTC75, which was phenotypically consistent with POT1 knocking down. Moreover, miR-185 accelerated the replicative senescence process in primary human fibroblasts in a POT1-dependent manner. Interestingly, increased serum miR-185 could ...Continue Reading

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Citations

May 4, 2021·Frontiers in Cell and Developmental Biology·Yang LiuQiang Liu
Aug 28, 2021·Biomedicines·Yousra HamdanGabriel Malka
Sep 7, 2021·Journal of the Egyptian National Cancer Institute·Gabriel Arantes Dos SantosMiguel Srougi

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Methods Mentioned

BETA
PCR
Assay
serum collection

Software Mentioned

ENCORI
miRanda
starBase
AxioVision LE

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