miRNA-21 and miRNA-34a Are Potential Minimally Invasive Biomarkers for the Diagnosis of Pancreatic Ductal Adenocarcinoma

Alemar, Bárbara; Izetti, Patrícia; Gregório, Cleandra; Macedo, Gabriel S.; Castro, Mauro A. A.; Osvaldt, Alessandro Bersch; Matte, Úrsula; Ashton‐Prolla, Patrícia

doi:10.1097/mpa.0000000000000383

Cited by 61 publications

(61 citation statements)

References 54 publications

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“…A previous study proposed that miR-34a is a potentially useful marker for the diagnosis of PDAC [8]. Our study demonstrated that lower miR-34a levels correlate with severe clinical symptoms and poor prognosis in PDAC patients.…”

Section: Discussionmentioning

confidence: 47%

“…However, most of the functional roles and targets of miRNAs have not been identified. Reduced expression of miR-34a is associated with poor overall survival in PDAC patients following resection [7] and serum miR-34a levels are potential diagnostic biomarkers of PDAC [8]. Exogenous overexpression of miR-34a inhibits the proliferation of cultured pancreatic cancer cells [9], sensitizes MiaPaCa2 pancreatic cancer cells to chemo- and radiotherapy by downregulating Bcl-2, Notch1 and Notch2 expression [10].…”

Section: Introductionmentioning

confidence: 99%

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The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

et al. 2016

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Background: Pancreatic ductaladenocarcinoma (PDAC) exhibits poor prognosis and resistance to chemotherapy. This study was to identify the biomarkers associated with the progression, poor prognosis and chemoresistance of PDAC. Methods: miR-34a and miR-150 levels in the plasma and tissues from PDAC patients were measured by real-time PCR. Xenograft PDAC tumor models were established in mice by inoculation of CD133+ stem cells isolated from PDAC tumors. Protein expression was measured by Western blot. Results: The plasma miR-34a and miR-150 levels were significantly lower in PDAC patients than in patients with benign pancreatic lesions and in healthy subjects. The miR-34a and miR-150 levels in the tumor tissues were significantly lower than in pancreatic tissues with benign lesions. The protein levels of CD133, Notch1, Notch2 and Notch4 receptors in PDAC tumor tissues were significantly higher than in pancreatic tissues with benign lesions. miR-34a injection significantly inhibited the tumor growth of PDAC tumors and sensitized the anticancer effects of 5-fluorouracil (5-FU). miR-34a significantly inhibited Notch1, Notch2 and Notch4 expression in xenograft tumor tissues in vivo and BxPC-3 cells in vitro. miR-34a and miR-150 significantly induced apoptosis and inhibited proliferation, invasion and migration in BxPC-3 cells. miR-34a, but not miR-150, significantly sensitized the anticancer effect of 5-FU in BxPC-3 cells in vitro. Conclusion: A loss of expression of miR-34a, but not of miR-150, is associated with disease progression and poor prognosis in PDAC patients, and may be involved in the chemoresistance of PDAC cells.

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Section: Discussionmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

et al. 2016

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“…However, miR-34a was found to be up-regulated in the serum of patients with PDAC. 155 The results obtained from the GEO database (accession numbers: GSE32688 and GSE15471) also indicated that miR-34a expression in PC was up-regulated. 156,157 The Role of miR-34a in the Proliferation of PC Several studied have explored the relationship between miR-34a and the proliferation of PC cells.…”

Section: Mir-34a Expression In Pcmentioning

confidence: 96%

“…The results showed that the expression level of miR-34a was closely related to the clinicopathological features of patients, suggesting that miR-34a may be used as a biomarker for the diagnosis and prognosis of PDAC. 155 Furthermore, CpG methylation of miR-34a was also employed as a diagnostic indicator for the prognosis of patients with PC. 164 Akamatsu et al 165 found that the expression level of miR-34a in serum could be used as a biomarker to distinguish between PDAC and autoimmune pancreatitis (AIP).…”

Section: The Role Of Mir-34a In the Diagnosis And Prognosis Of Pcmentioning

confidence: 99%

<p>A Systemic Review on the Regulatory Roles of miR-34a in Gastrointestinal Cancer</p>

Kong¹,

Wang²

2020

OTT

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MicroRNAs (miRNAs) are a class of endogenous non-coding single-stranded small-molecule RNAs that regulate gene expression by repressing target messenger RNA (mRNA) translation or degrading mRNA. miR-34a is one of the most important miRNAs participating in various physiological and pathological processes. miR-34a is abnormally expressed in a variety of tumors. The roles of miR-34a in gastrointestinal cancer (GIC) draw lots of attention. Numerous studies have demonstrated that dysregulated miR-34a is closely related to the proliferation, differentiation, migration, and invasion of tumor cells, as well as the diagnosis, prognosis, treatment, and chemo-resistance of tumors. Thus, we systematically reviewed the abnormal expression and regulatory roles of miR-34a in GICs including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), and gallbladder cancer (GBC). It may provide a profile of versatile roles of miR-34a in GICs.

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“…The role of miR-34a in regulating tumor biology has been extensively studied, while being an effective biomarker is another function of miR-34a. Serum miR-34a can be a potentially useful diagnostic biomarker of pancreatic ductal adenocarcinoma (73). Furthermore, miR-34a is likely to be involved in the treatment response of lung metastases of HCC to sorafenib (74).…”

Section: Gc-related Mirnasmentioning

confidence: 99%

Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer

Zhang

Duan

et al. 2015

Oncology Reports

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Gastric cancer is one of the most common malignant tumors worldwide; however, the efficacy of clinical treatment is limited. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been reported to play a key role in the development of cancer. They also provide novel candidates for targeted therapy. To date, in-depth studies on the molecular mechanisms of gastric cancer involving miRNAs are still absent. We previously reported that 5 miRNAs were identified as being significantly increased in gastric cancer, and the role of these miRNAs was investigated in the present study. By using bioinformatics tools, we found that more than 4,000 unique genes are potential downstream targets of gastric cancer miRNAs, and these targets belong to the protein class of nucleic acid binding, transcription factor, enzyme modulator, transferase and receptor. Pathway mapping showed that the targets of gastric cancer miRNAs are involved in the MAPK signaling pathway, pathways in cancer, the PI3K-Akt signaling pathway, the HTLV-1 signaling pathway and Ras signaling pathway, thus regulating cell growth, differentiation, apoptosis and metastasis. Analysis of the pathways related to miRNAs may provides potential drug targets for future therapy of gastric cancer.

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miRNA-21 and miRNA-34a Are Potential Minimally Invasive Biomarkers for the Diagnosis of Pancreatic Ductal Adenocarcinoma

Abstract: Serum miR-21 and miR-34a are potentially useful diagnostic biomarkers of PDAC. In addition, our results suggest that these miRNAs are not differentially expressed in saliva, making them unsuitable for use as noninvasive biomarkers for diagnostic purposes.

Cited by 61 publications

References 54 publications

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

<p>A Systemic Review on the Regulatory Roles of miR-34a in Gastrointestinal Cancer</p>

Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer

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