Exosomal miR-1255b-5p targets human telomerase reverse transcriptase in colorectal cancer cells to suppress epithelial-to-mesenchymal transition.

Molecular Oncology
Xue ZhangYunfeng Zhou

Abstract

Cancer cells undergo epithelial-to-mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms remain unclear. We identified a targeting relationship between tumor-suppressing miR-1255b-5p and human telomerase reverse transcriptase (hTERT) via clinical screening of serum samples in colorectal cancer (CRC) patients. EMT suppression via exosomal miR-1255b-5p delivery was investigated by assessing hTERT expression, Wnt/β-catenin signaling, and telomerase activity. We revealed that hypoxia directly affected exosomal miR-1255b-5p content, the delivery of which between CRC cells significantly impacted cell invasion, EMT-related protein expression, and telomerase stability. Specifically, miR-1255b-5p suppressed EMT by inhibiting Wnt/β-catenin activation via hTERT inhibition. Hypoxia reduced exosomal miR-1255b-5p secretion by CRC cells, thereby increasing hTERT expression to enhance EMT and telomerase activity. In a mouse CRC model, hypoxic exosomes containing overexpressed miR-1255b-5p attenuated EMT, tumor progression...Continue Reading

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Citations

Dec 22, 2020·Frontiers in Pharmacology·Linshen Xie, Ye Zeng
Apr 16, 2021·Pathology, Research and Practice·Soudeh Ghafouri-FardMohammad Taheri
Jun 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardMohammad Taheri

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Datasets Mentioned

BETA
GSE39833
AB085628.1

Methods Mentioned

BETA
transmission electron microscopy
transfection
PCR
Assay
xenograft
Fluorescence imaging
flow cytometry
xenografting

Software Mentioned

imagepro
bio
Ensembl
Tanon gis
TargetScan
imagej
Leica Application Suite
rad

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