A panel of serum exosomal microRNAs as predictive markers for chemoresistance in advanced colorectal cancer

Jin, Guoying; Liu, Yuhang; Jia, Zhang; Bian, Zehua; Yao, Surui; Fei, Bojian; Zhou, Leyuan; Yin, Yuan; Huang, Zhaohui

doi:10.1007/s00280-019-03867-6

Cited by 98 publications

(100 citation statements)

References 43 publications

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“…This is of translational relevance, considering that miR-21 is a well-established oncogenic miR whose major targets include the tumor suppressors PTEN and PDCD4 [30,31], both of which inhibit PI3K/AKT/mTOR signaling and the Wnt/β-catenin cascade [30,32]. Moreover, EV miR-21 was implicated in resistance of recipient cancer cells to anticancer therapeutics [12,33]; in agreement, our bioinformatics analysis showed that miR-21 was the most abundant miR encapsulated within salivary EVs from six patients with OSCC. Notably, we also provided evidence that PI3K, STAT3, mTOR, and TGF-β1 mRNA and protein expressions are upregulated in CSC_EVs, compared to EVs isolated from parental CAL27 and SCC-15 cells.…”

Section: Discussionmentioning

confidence: 99%

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Chen

Bamodu

et al. 2019

Cancers

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Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated Cancers 2020, 12, 56 2 of 16 β-catenin, phosphatidylinositol-3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and transforming growth factor (TGF)-β1 messenger (m)RNA and protein expression levels. CSC_EVs also conferred a cancer-associated fibroblast (CAF) phenotype on normal gingival fibroblasts (NGFs), with the resultant CAFs enhancing the oncogenicity of OSCC cells. Interestingly, treatment with ovatodiolide (OV), the bioactive component of Anisomeles indica, suppressed OSCC tumorigenesis by reducing the cargo content of EVs derived from CSCs, suppressing self-renewal, and inhibiting the NGF-CAF transformation by disrupting EV-TME interactions. Moreover, by suppressing miR-21-5p, STAT3, and mTOR expressions in CSC_EVs, OV re-sensitized CSCs to CDDP and suppressed OSCC tumorigenesis. In vivo, treatment with OV alone or in combination with CDDP significantly reduced the tumor sphere-forming ability and decreased EV cargos containing mTOR, PI3K, STAT3, β-catenin, and miR-21-5p. In summary, our findings provide further strong evidence of OV's therapeutic effect in OSCC.

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Section: Discussionmentioning

confidence: 99%

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Chen

Bamodu

et al. 2019

Cancers

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“…Additionally, the potential of miRNAs to treat CRC resistance is noteworthy. As described by Jin et al in 2019, the expression levels of miR-21-5p, miR-1246, miR-1229-5p, and miR-96-5p in the serum exosomes of the chemosensitive control group were lower than those of chemosensitive patients, suggesting that the above miRNAs of exosomes can predict the chemical resistance of CRC patients and are expected to be new targets for the treatment of drug resistance [137].…”

Section: Emerging Liquid Biopsy Markersmentioning

confidence: 68%

Perspectives of the Application of Liquid Biopsy in Colorectal Cancer

Ding

Wang

et al. 2020

BioMed Research International

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Colorectal cancer (CRC) is one of the most common gastrointestinal tumors and the second leading cause of cancer death worldwide. Since traditional biopsies are invasive and do not reflect tumor heterogeneity or monitor the dynamic progression of tumors, there is an urgent need for new noninvasive methods that can supplement and improve the current management strategies of CRC. Blood-based liquid biopsies are a promising noninvasive biomarker that can detect disease early, assist in staging, monitor treatment responses, and predict relapse and metastasis. Over time, an increasing number of experiments have indicated the clinical utility of liquid biopsies in CRC. In this review, we mainly focus on the development of circulating tumor cells and circulating tumor DNA as key components of liquid biopsies in CRC and introduce the potential of exosomal microRNAs as emerging liquid biopsy markers in clinical application for CRC.

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“…In addition, exosomal miR‐1229 derived from CRC cells promoted the tumor growth and angiogenesis by targeting HIPK2 (Hu et al, 2019). Similarly, the expression levels of exosomal miR‐1229‐3p were increased both in the culture media of chemoresistant CRC cells and the serum samples of chemoresistant CRC patients (Jin et al, 2019). A recent study showed that high plasma miR‐1229‐3p level was an independent poor prognostic factor for the recurrence‐free survival in GC.…”

Section: Discussionmentioning

confidence: 98%

A robust six‐miRNA prognostic signature for head and neck squamous cell carcinoma

Zhao

Cui

2020

Journal Cellular Physiology

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Head and neck squamous cell carcinoma (HNSCC) remains a major health problem worldwide. We aimed to identify a robust microRNA (miRNA)‐based signature for predicting HNSCC prognosis. The miRNA expression profiles of HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. The TCGA HNSCC cohort was randomly divided into the discovery and validation cohort. A miRNA‐based prognostic signature was built up based on TGCA discovery cohort, and then further validated. The downstream targets of prognostic miRNAs were subjected to functional enrichment analyses. The role of miR‐1229‐3p, a prognosis‐related miRNA, in tumorigenesis of HNSCC was further evaluated. A total of 305 significantly differentially expressed miRNAs were found between HNSCC samples and normal tissues. A six‐miRNA prognostic signature was constructed, which exhibited a strong association with overall survival (OS) in the TCGA discovery cohort. In addition, these findings were successfully confirmed in TCGA validation cohort and our own independent cohort. The miRNA‐based signature was demonstrated as an independent prognostic indicator for HNSCC. A risk signature‐based nomogram model was constructed and showed good performance for predicting the OS for HNSCC. The functional analyses revealed that the downstream targets of these prognostic miRNAs were closely linked to cancer progression. Mechanistically, in vitro analysis revealed that miR‐1229‐3p played a tumor promoting role in HNSCC. In conclusion, our study has developed a robust miRNA‐based signature for predicting the prognosis of HNSCC with high accuracy, which will contribute to improve the therapeutic outcome.

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A panel of serum exosomal microRNAs as predictive markers for chemoresistance in advanced colorectal cancer

Cited by 98 publications

References 43 publications

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Perspectives of the Application of Liquid Biopsy in Colorectal Cancer

A robust six‐miRNA prognostic signature for head and neck squamous cell carcinoma

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