Serum miR-20a is a promising biomarker for gastric cancer

Yang, Ruirui; Fu, Yun; Zeng, Ying; Xiang, Mengqin; Yin, Yufang; Li, Li; Xu, Hao; Zhong, Jing; Zeng, Xi

doi:10.3892/br.2017.862

Cited by 49 publications

(45 citation statements)

References 23 publications

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“…It was reported that miR-20a was highly expressed in hepatocellular carcinoma [43], lung cancer [44], colon cancer [45] and other tumors [46,47] and acts as an oncogene. And miR-20a can be used as a biomarker in the diagnosis and prognosis of GC [48,49]. Combination of the above studies and reports, it suggested that miR-20a-5p was the most possible candidate to regulate WTX expression and effect GC progression.…”

Section: Discussionmentioning

confidence: 99%

Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

Shen

et al. 2020

Preprint

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Background: The X-linked gene WTX (also called AMER1), has been reported to act as a tumor suppress gene in Wilms tumor. Our previous study reported that WTX expression was significantly reduced in gastric cancer (GC), but the function and mechanism of WTX loss had not been fully elucidated yet. Methods: WTX/miR-20a-5p expression was analyzed in paraffin-embedded archived GC tissues and validated in public databases. KEGG pathway analyses were performed to explore the mechanism of WTX in GC progression. The role of WTX/miR-20a-5p in cell growth, migration, invasion and angiogenesis was investigated in vitro and in vivo. Western blot, immunohistochemistry, RT-PCR, luciferase assay, and Co-immunoprecipitation (Co-IP) were used to detect the regulation of WTX and PI3K/AKT/mTOR signaling by miR-20a-5p.Results: We revealed that WTX served as a tumor suppressor whose loss associated with the aggressive feature of GC by showing hyperproliferation in vitro and high metastasis phenotype in vivo. And WTX expression level was positively correlated with the overall survival of GC patients. Microarray, bioinformatics analysis, and verification experiments showed that WTX loss activated PI3K/AKT/mTOR pathway, and promoted the proliferation and invasion of GC cells. We also discovered that the miR-20a-5P aberrant upregulation was one of the reasons inducing WTX loss in GC which stimulated PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway, thus promoted GC progression.Conclusions: This study unveiled the mechanism of GC progression which was, at least partially, caused by miR-20a-5p aberrant upregulation which inhibited WTX expression and thus activate PI3K/AKT/mTOR signaling pathway. It provided a comprehensive understanding of the action of miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

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Section: Discussionmentioning

confidence: 99%

Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

Shen

et al. 2020

Preprint

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“…miR-20a is an important molecule in a variety of biological processes and in cancer progression. Previous studies have shown that the serum exhibits high miR-20a expression and has been indicated to be associated with poor prognosis in patients with nasopharyngeal carcinoma and gastric cancer (44,45). A study has shown that miR-20a can directly target run-related transcription factor 1 to attenuate cell-death in cervical cancer cells by preventing natural killer (NK) cells from releasing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which promote tumor growth (46).…”

Section: Microrna-20a Overviewmentioning

confidence: 99%

Function and mechanisms of microRNA‑20a in colorectal cancer (Review)

et al. 2020

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Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-associated mortality worldwide. CRC currently has no specific biomarkers to promote its diagnosis and treatment and the underlying mechanisms regulating its pathogenesis have not yet been determined. MicroRNAs (miRs) are small, non-coding RNAs that exhibit regulatory functions and have been demonstrated to serve a crucial role in the post-transcriptional regulatory processes of gene expression that is associated with cell physiology and disease progression. Recently, abnormal miR-20a expression has been identified in a number of cancers types and this has become a novel focus within cancer research. High levels of miR-20a expression have been identified in CRC tissues, serum and plasma. In a recent study, miR-20a was indicated to be present in feces and to exhibit a high sensitivity to CRC. Therefore, miR-20a may be used as a marker for CRC and an indicator that can prevent the invasive examination of patients with this disease. Changes in the expression of miR-20a during chemotherapy can be used as a biomarker for monitoring resistance to treatment. In conclusion, miR-20a exhibits the potential for clinical application as a novel diagnostic biomarker and therapeutic target for use in patients with CRC. The present study focused on the role and mechanisms of miR-20a in CRC. Contents 1. Introduction 2. microRNA-20a overview 3. The mechanism of miR-20a in CRC 4. miR-20a can be used as a diagnostic marker in CRC 5. miR-20a may be used as a monitoring indicator during chemotherapy 6. Conclusion and prospects

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“…The observed in our study negative correlation of TIMP3 with miR-20a expression (both preoperative and postoperative miR20a in SCC subtype, post miR20a in the entire study cohort), can be explained as epigenetic silencing of the genes controlling the ECM remodeling. The miR-20a action has been previously linked to the induction of vascular changes in invasive breast carcinomas (48) and metastasis in gastric cancer (50). TIMP3 silencing mediated by miR-20a may be treated as a hallmark of substantial ECM deregulation already present in the NLNT.…”

Section: The Correlations Of Gene and Mir Expressionmentioning

confidence: 99%

A Strong Decrease in TIMP3 Expression Mediated by the Presence of miR-17 and 20a Enables Extracellular Matrix Remodeling in the NSCLC Lesion Surroundings

et al. 2019

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Background: Lung cancer is one of the most common causes of death worldwide with a relatively high fatality rate and a mean 5-years survival of about 18%. One of the hallmarks of cancer is the extracellular matrix (ECM) remodeling, which is crucial for metastasis. This process may be regulated by miRs targeting metalloproteinases (MMPs) associated with the ECM breakdown and metastatic process or blocking the action of tissue inhibitors of metalloproteinases (TIMPs). Search for early biomarkers is essential in detecting non-small cell lung cancer (NSCLC) and distinguishing its subtypes: Adenocarcinoma (AC) from Squamous Cell Carcinoma (SCC), enabling targeted chemotherapy.Methods: MiR-17 and miR-20a targeting MMP2 and TIMP3 were selected by TCGA data analysis with further validation using miRTarBase and literature. The study group comprised 47 patients with primary NSCLC (AC and SCC subtypes). RNA was isolated from the tumor and normal-looking neighboring tissue (NLNT) free of cancer cells. MiRs from peripheral blood exosomes were extracted on admission and 5-7 days after surgery. Gene and miRs expression were assessed in qPCR using TaqMan probes. Results:The MMP2 has been expressed on a similar level in NLNT, as in cancer. While, TIMP3 expression was decreased both in cancer tissue and NLNT, with significantly lower expression in cancer. TIMP3 downregulation in NLNT and in SCC subtype correlated negatively with miR-20a. The preoperative miR-17 expression was significantly higher among patients with SCC compared to AC. Receiver operating characteristic (ROC) analysis of miR-17 as AC subtype classifier revealed 90% specificity and 48% sensitivity in optimal cut-off point with area under ROC curve (AUC): 0.71 (95%CI: 0.55-0.87). Within NSCLC subtypes: a strong negative correlation between pack-years (PY) and TIMP3 expression was observed for NLNT in the SCC group. Czarnecka et al. ECM Remodeling in NSCLC Conclusion:The TIMP3 silencing observed in the NLNT and its negative correlation with presurgical expression of miR-20a (from serum exosomes), suggest that miRs can influence ECM remodeling at a distance from the center of the lesion. The miRs expression pattern in serum obtained before surgery significantly differs between AC and SCC subtypes. Moreover, decreased TIMP3 expression in NLNT (in SCC group) negatively correlates with the amount of tobacco smoked in a lifetime in PY.Keywords: NSCLC molecular diagnostic markers, miRNA regulation, microRNA, extracellular matrix remodeling, metalloproteinases, tissue inhibitors of metalloproteinases, exosomes absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Serum miR-20a is a promising biomarker for gastric cancer

Cited by 49 publications

References 23 publications

Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

Function and mechanisms of microRNA‑20a in colorectal cancer (Review)

A Strong Decrease in TIMP3 Expression Mediated by the Presence of miR-17 and 20a Enables Extracellular Matrix Remodeling in the NSCLC Lesion Surroundings

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