Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

Liu, Xiangxiang; Pan, Bei; Sun, Li; Chen, Xiaoxiang; Zeng, Ke; Hu, Xiuxiu; Xu, Tan; Xu, Mu; Wang, Shukui

doi:10.1158/1055-9965.epi-18-0067

Cited by 104 publications

(64 citation statements)

References 37 publications

(36 reference statements)

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“…Previous research has established that miR-27a-3p is implicated in the biological behavior of tumor cells in numerous cancer types. [29][30][31] Although research has also suggested that changes in miR-27a-3p expression are associated with the chemosensitivity of various malignancies, [32][33][34] the specific role that miR-27a-3p plays in the regulation of ADR resistance in BC has not been well established. Further research regarding the mechanisms of ADR resistance are needed so that effective agents can be developed to reverse chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

<p>MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells</p>

Zhu¹,

Chen²,

Fu³

et al. 2020

OTT

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Aim: This study aimed to explore the regulative mechanisms of miR-27a-3p in chemoresistance of breast cancer cells. Materials and Methods: qRT-PCR was employed to determine miR-27a-3p expression in two breast cancer cell lines, MCF-7 and MCF-7/adriamycin-resistant cell line (MCF-7/ADR). The two cell lines were treated with miR-27a-3p mimics or inhibitors or corresponding negative control (NC), respectively. The changes were investigated by qRT-PCR, CCK-8 assay, Western blot (WB), colony formation assay, and flow cytometry assay. Moreover, luciferase reporter assay was analyzed to verify the downstream target gene of miR-27a-3p. Further investigation in the correlation between miR-27a-3p and BTG2 was launched by WB, flow cytometry assay, and CCK-8 assay. The expression of Akt and p-Akt was detected by WB. Key Findings: Significantly higher miR-27a-3p expression was confirmed in MCF-7/ADR as compared with sensitive cell line MCF-7 (P<0.05). The down-regulation of miR-27a-3p in MCF-7/ADR enhanced the sensitivity of cancer cells to adriamycin treatment, decreased multidrug resistance gene 1/P-glycoprotein (MDR1/P-gp) expression, enhanced the apoptosis-related proteins expression, increased adriamycin-induced apoptosis, and inhibited cell proliferation as compared to NC groups (P<0.05). The up-regulation of miR-27a-3p in MCF-7 showed the opposite results. BTG2 is identified as a direct target of miR-27a-3p and its down-regulation reversed ADR-resistance. BTG2 treatment exhibited inhibitory effect on PI3K/Akt pathway in MCF-7/ADR cells. Significance: miR-27a-3p might be associated with resistance of breast cancer cells to adriamycin treatments, modulating cell proliferation and apoptosis by targeting BTG2 and promoting the PI3K/Akt pathway in breast cancer cells. miR-27a-3p/BTG2 axis might be a potential therapeutic target for clinical BC resistance.

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Section: Discussionmentioning

confidence: 99%

<p>MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells</p>

Zhu¹,

Chen²,

Fu³

et al. 2020

OTT

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“…The aberrant over‐expression of miR‐27a has also been identified in the exosomal species from cancer patients by several independent investigations. Liu et al . first proposed that circulating miR‐27a and miR‐130a served as potential prognostic and diagnostic biomarkers in colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Geng

Liu

et al. 2020

The Journal of Gene Medicine

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Background:The tumor suppressor role of tissue factor pathway inhibitor 2 (TFPI-2) has been reported in various tumors. The present study aimed to improve the understanding of the oncogenic properties of TFPI-2 in gastric cancer. Methods:Relative expression of TFPI-2 was determined by a real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell viability was measured via a cell counting kit-8 assay and proliferation was evaluated by a colony formation assay. Cell apoptosis was assessed with a caspase-3 activity kit and invasion was evaluated by a transwell chamber assay. The methylation level of TFPI-2 promoter was assayed by methylation-specific PCR. The regulatory effect of miR-27a-3p on TFPI-2 was analyzed with a luciferase reporter assay. The direct association between miR-27a-3p and TFPI-2 was shown by biotin-labelling pulldown.Results: TFPI-2 was down-regulated in gastric cancer, which associated with an unfavorable prognosis clinically. Ectopic introduction of TFPI-2 greatly compromised cell viability, colony formation and invasive capacity, and also induced cell apoptosis simultaneously. The promoter region of TFPI-2 was extensively methylated in gastric cancer tissues compared to normal tissues, suggesting the epigenetic inhibition of TFPI-2 expression. We further identified that TFPI-2 functioned as sponge RNA against miR-27a-3p. Most importantly, miR-27a-3p-specific inhibitor significantly exerted a tumor suppressor function akin to TFPI-2 itself, and the anti-tumoral activities were completely abolished by TFPI-2 knockdown. Conclusions:We found that the epigenetically suppressed TFPI-2 compromised sponging effects with respect to miR-27a-3p in gastric cancer, which consequently and mechanistically contributed to the tumor biology of gastric cancer. K E Y W O R D Sgastric cancer, methylation, miR-27a-3p, TFPI-2 Geng and Liu contributed equally to this work.

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“…These vesicles, loaded with proteins and unique RNAs, have a wide range of biological functions, such as cell-to-cell communication [18]. Our previous study showed that circulating exosomal miR-27a and miR-130a were novel diagnostic and prognostic biomarkers of CRC [19]. However, specific miRNAs in serum exosome associated with LM have not been adequately investigated in CRC.…”

Section: Ivyspringmentioning

confidence: 99%

Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis

Sun¹,

Liu²,

Pan³

et al. 2020

J. Cancer

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Background: Liver is the most common site for metastatic spread of CRC at the time of diagnosis which leads to high mortality. This study aimed to identify novel circulating exosomal miRNAs as biomarkers of colorectal cancer (CRC) with liver metastasis (LM). Materials and methods: Candidate miRNAs were selected through integrated analysis of Gene Expression Omnibus (GEO) database as well as clinical samples. Exosomes isolated from serum and cultured media were identified by using transmission electron microscopy (TEM) and western blot. The expression levels and diagnostic value of candidate miRNAs were further tested and validated through qRT-PCR and receiver operating characteristic curve (ROC) analysis. The association of candidate miRNA expressions with patients' prognosis was analyzed with logistic regression and Cox proportional hazards regression models. Results: After integrated analysis of three GEO datasets and clinical samples, miR-122 was discovered to be remarkably overexpressed in tissues of CRC patients. Then we revealed that elevated serum miR-122 was tumor-derived by being packaged into exosomes. The expressions of serum exosomal miR-122 were significantly upregulated in CRC patients, especially in those with LM. Serum exosomal miR-122 expressions could differentiate CRC patients with LM from healthy controls and patients without LM with area under the ROC curve (AUC) of 0.89 and 0.81. Uni-and multivariate logistic regression showed that serum exosomal miR-122 was an independent prognostic indicator of CRC patients. Conclusions: Serum exosomal miR-122 was a novel potential diagnostic and prognostic biomarker in CRC patients with LM.

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Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

Cited by 104 publications

References 37 publications

<p>MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells</p>

<p>MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells</p>

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis

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