&lt;p&gt;MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1&lt;/p&gt;

Chen, Zhimin; Qiao, Yu; Chen, Gang; Tang, Rongjiang; Luo, Dianzhong; Dang, Yi-Wu; Wei, Dan‐Ming

doi:10.2147/cmar.s199257

Cited by 19 publications

(14 citation statements)

References 39 publications

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“…In our study, we also observed reduction of KRAS expression by miR‐193a‐3p overexpression and confirmed that miR‐193a‐3p directly targets the 3′‐UTR of KRAS mRNA, which is consistent with previous reports 28,29 . In addition to KRAS , the following genes have been reported as direct targets of miR‐193a‐3p: Mcl1 in ovarian cancer 38 and glioblastoma 39 ; Cyclin D1 in breast, 40 prostate, 41 gastric, 42 thyroid, 43 and pancreatic cancers 44 ; and CDK4 and CDK6 in breast cancer 40 . To the best of our knowledge, this is the first study to show that miR‐193a‐3p overexpression also decreases the expressions of Mcl1, Cyclin D1, CDK4, and CDK6 proteins in CRC, although whether the regulation by miR‐193a‐3p is via directly targeting the 3’‐UTR of mRNAs also in CRC requires further elucidation.…”

Section: Discussionsupporting

confidence: 92%

Tumor suppressor miR‐193a‐3p enhances efficacy of BRAF/MEK inhibitors in BRAF‐mutated colorectal cancer

et al. 2021

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Patients with BRAF‐mutated colorectal cancer (CRC) have a poor prognosis despite recent therapeutic advances such as combination therapy with BRAF, MEK, and epidermal growth factor receptor (EGFR) inhibitors. To identify microRNAs (miRNAs) that can improve the efficacy of BRAF inhibitor dabrafenib (DAB) and MEK inhibitor trametinib (TRA), we screened 240 miRNAs in BRAF‐mutated CRC cells and identified five candidate miRNAs. Overexpression of miR‐193a‐3p, one of the five screened miRNAs, in CRC cells inhibited cell proliferation by inducing apoptosis. Reverse‐phase protein array analysis revealed that proteins with altered phosphorylation induced by miR‐193a‐3p were involved in several oncogenic pathways including MAPK‐related pathways. Furthermore, overexpression of miR‐193a‐3p in BRAF‐mutated cells enhanced the efficacy of DAB and TRA through inhibiting reactivation of MAPK signaling and inducing inhibition of Mcl1. Inhibition of Mcl1 by siRNA or by Mcl1 inhibitor increased the antiproliferative effect of combination therapy with DAB, TRA, and anti‐EGFR antibody cetuximab. Collectively, our study demonstrated the possibility that miR‐193a‐3p acts as a tumor suppressor through regulating multiple proteins involved in oncogenesis and affects cellular sensitivity to MAPK‐related pathway inhibitors such as BRAF inhibitors, MEK inhibitors, and/or anti‐EGFR antibodies. Addition of miR‐193a‐3p and/or modulation of proteins involved in the miR‐193a‐3p–mediated pathway, such as Mcl1, to EGFR/BRAF/MEK inhibition may be a potential therapeutic strategy against BRAF‐mutated CRC.

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Section: Discussionsupporting

confidence: 92%

Tumor suppressor miR‐193a‐3p enhances efficacy of BRAF/MEK inhibitors in BRAF‐mutated colorectal cancer

et al. 2021

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“…The diagnostic efficiency of circulating miR-1290 and miR-1246 were tested in various cancers, including non-small cell lung cancer, prostate cancer and PC [11,21,[25][26][27][28]. Serum miR-1290 had superior ability to identify PC patients than serum miR-1246 and CA19-9, which was in agreement with the findings of Li et al [21].…”

Section: Discussionsupporting

confidence: 78%

“…Moreover, they are highly conserved, tissue-specific and keep stable in body fluids, which make it possible to monitor diseases through miRNA analysis [9]. It was reported that the upregulation of miR-21-5p, miR-193a-3p, miR-221-3p, miR-99 and miR-155 was associated with initiation and progression of PC, as well as resistance to chemotherapy [10][11][12][13][14], whereas they were not always of high diagnostic value and further studies are required to identify promising miRNA signatures in blood circulation for PC diagnosis.…”

Section: Ivyspringmentioning

confidence: 99%

Serum miR-1290 and miR-1246 as Potential Diagnostic Biomarkers of Human Pancreatic Cancer

Wei¹,

Yang²,

Wu³

et al. 2020

J. Cancer

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Background: Pancreatic cancer (PC) is a highly malignant tumor with no effective early diagnostic biomarkers. This study was performed to screen and identify serum microRNAs (miRNAs) as noninvasive biomarkers for PC diagnosis. Methods: Two upregulated miRNAs were selected by integrated analysis of three independent GEO datasets. Then, the expressions of two miRNAs in serum were determined by quantitative reverse-transcription PCR among 120 PC patients, 40 benign disease controls and 40 healthy controls. The correlation between serum miRNAs and clinical characteristics was analyzed. The diagnostic utility of miRNAs was compared to CA19-9 using receiver operating characteristic curve analysis. Results: We discovered miR-1290 and miR-1246 were upregulated in PC patients through GEO datasets analysis. Serum miR-1290 and miR-1246 expression levels were elevated in PC patients compared to all controls and dramatically decreased after tumor resection (all P<0.001). The area under the curve (AUC) for miR-1290 was larger than miR-1246 and CA19-9 (miR-1290: 0.91; miR-1246: 0.81; CA19-9: 0.82). The combined diagnosis of individual or both miRNAs with CA19-9 was more effective for discriminating PC from all controls than the single CA19-9 assay

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“…Radulovich et al uncovered that the overexpression of CCND1 is most common in PDAC and occurred mainly in late-stage pancreatic intraepithelial neoplastic (PanIN) lesions [ 46 ]. In addition, Chen et al revealed that CCND1 was targeted by miR-193a-3p, and overexpression of miR-193a-3p significantly decreased CCND1 expression to inhibit the tumor growth in PDAC cells [ 47 ]. CCND1 may be one of the abnormally methylated genes, which have been indicated as proto-oncogenes that are positively associated with lymph node metastasis, regulating G1-to-S phase progression in human tumors [ 48 – 50 ].…”

Section: Discussionmentioning

confidence: 99%

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

Zhu

Zhou

Zhu

et al. 2021

Mediators of Inflammation

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Emerging evidence has shown that circular RNAs (circRNAs) and DNA methylation play important roles in the causation and progression of cancers. However, the roles of circRNAs and abnormal methylation genes in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. Expression profiles of circRNA, gene methylation, and mRNA were downloaded from the GEO database, and differentially expressed genes were obtained via GEO2R, and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Inflammation-associated genes were collected from the GeneCards database. Then, functional enrichment analysis and protein-protein interaction (PPI) networks of inflammation-associated methylated expressed genes were investigated using Metascape and STRING databases, respectively, and visualized in Cytoscape. Hub genes of PPI networks were identified using the NetworkAnalyzer plugin. Also, we analyzed the methylation, protein expression levels, and prognostic value of hub genes in PDAC patients through the UALCAN, Human Protein Atlas (HPA), and Kaplan-Meier plotter databases, respectively. The circRNA_102049/miR-455-3p/CD80 axis was identified by the ceRNA network and hub genes. In vitro and in vivo experiments were performed to evaluate the functions of circRNA_102049. The regulatory mechanisms of circRNA_102049 and miR-455-3p were explored by RT-PCR, western blot, and dual-luciferase assays. In the present study, twelve hub genes (STAT1, CCND1, KRAS, CD80, ICAM1, ESR1, RAF1, RPS6KA2, KDM6B, TNRC6A, FOSB, and DNM1) were determined from the PPI networks. Additionally, the circRNA_102049 was upregulated in PDAC cell lines. Functionally, the knockdown of circRNA_102049 by siRNAs inhibited cell growth, inflammatory factors, and migratory and invasive potential and promoted cell apoptosis. Mechanistically, circRNA_102049 functioned as a sponge of miR-455-3p and partially reversed the effect of miR-455-3p and consequently upregulated CD80 expression. Our findings showed that circRNA_102049 and methylated hub genes play an important role in the proliferation, apoptosis, migration, invasion, and inflammatory response of PDAC, which might be selected as a promising prognostic marker and therapeutic target for PDAC.

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<p>MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1</p>

Cited by 19 publications

References 39 publications

Tumor suppressor miR‐193a‐3p enhances efficacy of BRAF/MEK inhibitors in BRAF‐mutated colorectal cancer

Tumor suppressor miR‐193a‐3p enhances efficacy of BRAF/MEK inhibitors in BRAF‐mutated colorectal cancer

Serum miR-1290 and miR-1246 as Potential Diagnostic Biomarkers of Human Pancreatic Cancer

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

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