Exosome-derived microRNAs contribute to prostate cancer chemoresistance

Li, Jing; Yang, Xin; Guan, Hao; Mizokami, Atsushi; Keller, Evan T.; Xu, Xiaozhen; Liu, Xia; Tan, Jiyong; Hu, Longyuan; Lü, Yi; Zhang, Jian

doi:10.3892/ijo.2016.3560

Cited by 74 publications

(48 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our research revealed that tumor cells can transfer miR-222 to other cells via exosomes to increase malignancy; these results are different from those of some other studies [42]. First, we screened miR-222 in tumor exosomes rather than in tumor tissue, and the experimental cell lines were highly metastatic daughter cells of the control cells.…”

Section: Discussioncontrasting

confidence: 90%

Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer

Yang

Wang

et al. 2018

Cell Physiol Biochem

100

View full text Add to dashboard Cite

Background/Aims: MicroRNAs (miRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal miRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. We aimed to investigate the detailed roles and mechanisms of tumor-generated exosomal miRNAs in progression of PDAC. Methods: miR-222 was identified by miRNA microarray studies in exosomes of PDAC cells, and further analyzed in plasma exosomes of PDAC patients. The regulatory mechanisms of miR-222 were explored by qRT-PCR, WB, dual-luciferase assays and immunofluorescence or confocal analysis. Other biological assays include transwell, xenograft models and so on. Results: miR-222 is significantly high in tumor exosomes or highly invasive PDAC cells. miR-222 could directly regulate p27 to promote cell invasion and proliferation. miR-222 could also activate AKT by inhibiting PPP2R2A expression, thus inducing p27 phosphorylation and cytoplasmic p27 expression to promote cell survival, invasion and metastasis. Expressions of miR-222 and p27 were significantly inversely correlated, and cytoplasmic p27, instead of nuclear p27, was associated with tumor malignancy. miR-222 could be transmitted between PDAC cells via exosome communication, and the exosomal miR-222 communication is functional. Plasma exosomal miR-222 in PDAC patients was high and significantly correlated to tumor size and TNM stage, and was an independent risk factor for PDAC patient survival. Conclusion: Tumor-generated exosomes could promote invasion and proliferation of neighboring tumor cells via miR-222 transmission, the plasma exosomal miR-222 plays important roles and may be a useful prognostic maker in PDAC.

show abstract

Section: Discussioncontrasting

confidence: 90%

Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer

Yang

Wang

et al. 2018

Cell Physiol Biochem

100

View full text Add to dashboard Cite

show abstract

“…In essence, over 10% of all reported research findings of miRNA influences in cancer chemoresistance demonstrated that such a phenotype modulation was effected through simultaneous dysregulation of multiple miRNAs, rather than an individual putative chemoresistance miRNA—though no specific miRNA combination was identified as most prevalent by the authors [44,46,47,48,49,62,67,71,76,81,85,88,132,133,158,168,201,203,211,212,213,217,223,224,228,230]. This suggests that miRNA influences on cellular functions also occur at a more complex level, whereby it is a signature dysregulated expression pattern of two (or more) miRNAs that trigger simultaneous downregulation of a specific set of target transcripts leading to an ultimate change in cellular/tissue phenotype.…”

Section: Influences Of Mirnas In Cancer Chemoresistancementioning

confidence: 99%

“…In addition to the effect of multiple miRNAs on cancer chemoresistance, several studies reported the possible influences exhibited by circulating miRNAs (in blood), typically through extracellular vesicle or exosome transport [67,168,172,205,228]. …”

Section: Influences Of Mirnas In Cancer Chemoresistancementioning

confidence: 99%

“…Exosome transfer was also identified as being implicated in chemoresistance conferring to prostate cancer, as highlighted by the investigation by Li and colleagues [228]. The study identified 29 dysregulated miRNAs within exosomes derived from two paclitaxel resistant prostate cancer cell line models [228].…”

Section: Influences Of Mirnas In Cancer Chemoresistancementioning

confidence: 99%

See 1 more Smart Citation

Influence of microRNAs and Long Non-Coding RNAs in Cancer Chemoresistance

Ayers

Vandesompele

2017

Genes

100

View full text Add to dashboard Cite

Innate and acquired chemoresistance exhibited by most tumours exposed to conventional chemotherapeutic agents account for the majority of relapse cases in cancer patients. Such chemoresistance phenotypes are of a multi-factorial nature from multiple key molecular players. The discovery of the RNA interference pathway in 1998 and the widespread gene regulatory influences exerted by microRNAs (miRNAs) and other non-coding RNAs have certainly expanded the level of intricacy present for the development of any single physiological phenotype, including cancer chemoresistance. This review article focuses on the latest research efforts in identifying and validating specific key molecular players from the two main families of non-coding RNAs, namely miRNAs and long non-coding RNAs (lncRNAs), having direct or indirect influences in the development of cancer drug resistance properties and how such knowledge can be utilised for novel theranostics in oncology.

show abstract

“…MicroRNAs (miR), as a key regulator, have been implicated as regulators controlling diverse biological processes at the post-transcriptional level of repression (3,4). Previously published studies explained that the excessive expression of miR-146a influenced the PCa cells in terms of apoptosis, progression, and viability by directly targeting the epidermal growth factor receptor (EGFR) (5), Ras-related C3 botulinum toxin substrate 1 (Rac1) (6), ROCK1 (7), interleukin-1 receptor-associated kinase 1 (IRAK1), and tumor necrosis factor receptor-associated factor 6 (TRAF6) (8).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer

Huang

Tao

Liu

et al. 2017

International Journal of Oncology

View full text Add to dashboard Cite

Previously published studies explained that the excessive expression of miR-146a influences the prostate cancer (PCa) cells in terms of apoptosis, progression, and viability. Although miR-146a acts as a tumor suppressor, current knowledge on the molecular mechanisms that controls its expression in PCa is limited. In this study, gene set enrichment analysis (GSEA) showed negatively enriched expression of miR-146a target gene sets and positively enriched expression of gene sets suppressed by the enhancer of zeste homolog 2 (EZH2) after YY1 depletion in PCa cells. The current results demonstrated that the miR-146a levels in PCa tissues with high Gleason scores (>7) are significantly lower than those in PCa tissues with low Gleason scores (≤7), which were initially observed in the clinical specimens. An inverse relationship between YY1 and miR-146a expression was also observed. Experiments indicated the decrease in cell viability, proliferation, and promoting apoptosis after YY1 depletion, while through inhibiting miR-146a could alleviate the negative effect brought by YY1 depletion. We detected the reversed adjustment of YY1 to accommodate miR-146a transcriptions. On the basis of YY1 depletion, we determined that the expression of miR-146a increased after EZH2 knockdown. We validated the combination of YY1 and its interaction with EZH2 at the miR-146a promoter binding site, thereby prohibiting the transcriptional activity of miR-146a in PCa cells. Our results suggested that YY1 depletion repressed PCa cell viability and proliferation and induced apoptosis at least in a miR-146a-assisted manner.

show abstract

Exosome-derived microRNAs contribute to prostate cancer chemoresistance

Cited by 74 publications

References 45 publications

Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer

Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer

Influence of microRNAs and Long Non-Coding RNAs in Cancer Chemoresistance

Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer

Contact Info

Product

Resources

About