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

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, and liver metastasis. Our results suggest the antitumor role of miR-1255b-5p and its involvement in the regulation of hTERT-mediated EMT. We propose that miRNA-targeted regulation of telomerase is a promising therapeutic strategy for future CRC treatment.

Nanoapproaches to Modifying Epigenetics of Epithelial Mesenchymal Transition for Treatment of Pulmonary Fibrosis

“…In survivors, radiographic evidence of pulmonary scarring ( Shi et al, 2020 ) and functional defects in lung function (diffusion capacity) are commonly seen ( Mo et al, 2020 ; Shi et al, 2020 ; Wang et al, 2020 ). In fatal cases, increases in the TGF-ECM networks, including upregulated TGFBR2, COL isoforms, and FN (12) are seen, and pulmonary fibrosis is found upon an autopsy ( Zhang T. et al, 2020 ). These data suggest that fibrosis and impaired pulmonary function is a sequelae of severe COVID-19-ARDS infections.…”

“…This includes for intrauterine adhesion ( Yao et al, 2019 ), liver fibrosis ( Li et al, 2012 ), acute lung injury (ALI) ( Xiao et al, 2020 ), and cancer [including colorectal ( Zhang X. et al, 2020 ), liver ( Chen et al, 2018 ), thyroid ( Hardin et al, 2018 ), and lung ( Zhao et al, 2018 )]. In the majority of these studies, MSC-derived exosomes were used [including from bone marrow ( Yao et al, 2019 ) and umbilical cord ( Li et al, 2012 ; Zhao et al, 2018 )], though others involved exosomes derived directly from carcinomas ( Chen et al, 2018 ; Zhang X. et al, 2020 ) or stem-like cells ( Hardin et al, 2018 ). Like inorganic NPs, most of the exosomes involved no additional API and instead relied on the intrinsic EMT-inhibition of the derived surface proteins.…”

“…Like inorganic NPs, most of the exosomes involved no additional API and instead relied on the intrinsic EMT-inhibition of the derived surface proteins. However, one exception did utilize the additional delivery of an exosomal miRNA ( Zhang X. et al, 2020 ). In all instances, EMT inhibition was achieved through the regulation of key biomarkers, including VIM, TGF-β, Smad2/3, FSP-1, E-Cadherin, CK19, NF-κB, ERK, JNK, and the Akt and hedgehog pathways.…”

Therapeutic Potential of Exosomes in Pulmonary Fibrosis

“…Exosomes can also inhibit EMT through their cargos. Exosomal miR-1255b-5p can suppress the EMT of colorectal cancer cells by inhibiting Wnt/β-catenin activation (Zhang et al, 2020), while exosomal miR-34c from mesenchymal stem cells can inhibit the EMT of nasopharyngeal carcinoma cells by targeting β-catenin (Wan et al, 2020). In another study, MSC-derived exosomal miR-3940-5p was shown to inhibit the EMT of colorectal cancer by targeting integrin alpha6 (ITGA6) (Li et al, 2020d), while exosomal miRNA-215-5p in adipose-derived stem cells inhibited the EMT of podocytes by inhibiting ZEB2 (Jin et al, 2020).…”

The potential roles of exosomal noncoding RNAs in osteosarcoma

“…These Exos participate in cell‐to‐cell communication in the tumor microenvironment and exert a vital effect in tumor biology (Cheng et al, 2020; Y. Li et al, 2019; Yi et al, 2020). Exo‐miR‐1255b‐5p targets human TERT in colorectal cancer (CRC) cells to suppress epithelial–mesenchymal transition (EMT; Zhang, Bai, et al, 2020). Qiu et al (2020) disclosed that exo‐miR‑146a originating from MSCs increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2‑mediated phosphatidylinositol 3‑kinase/protein kinase B axis.…”