Exosomal microRNA in Pancreatic Cancer Diagnosis, Prognosis, and Treatment: From Bench to Bedside

Uddin, Md. Hafiz; Hallak, Mohammed Najeeb Al; Philip, Philip A.; Mohammad, Ramzi M.; Viola-Villegas, Nerissa; Wagner, Kay Uwe; Azmi, Asfar S.

doi:10.3390/cancers13112777

Cited by 27 publications

(15 citation statements)

References 190 publications

(250 reference statements)

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“…MiRNA has its specific expression spectrum, and it is reported that extracellular miRNAs can circulate in the bloodstream being remarkably stable [2]. They have been studied as markers of many diseases since its discovery, mostly in cancers like pancreatic cancer and breast cancer [3][4][5]. In recent years, several literatures have reported that microRNA-146 (miR-146) may play an important role in the pathological process of RA and may be a diagnostic marker of RA.…”

Section: Introductionmentioning

confidence: 99%

Upregulated miR-146a Expression in Peripheral Blood Relates to Th17 and Treg Imbalance in Elder Rheumatoid Arthritis Patients

et al. 2022

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Background: The expression level of microRNA-146a (miR-146a) increased in peripheral blood and synovialis tissue of rheumatoid arthritis (RA) patient, it may play an important role in the pathological process of RA. We investigated its possibility as a diagnostic marker and the correlation with Th17 and Treg cells in elder RA patients. Methods: Blood samples were collected from 38 active RA patients, 38 inactive RA patients, and 40 healthy controls. RNA expression levels of miR-146a were detected from the peripheral blood samples. The proportion of Th17 and Treg cells were analyzed, as well as their cell-specific transcription factor retinoic acid-related orphan receptor variant 2 (RORc) and forkhead box protein 3 (FOXP3). Furthermore, secretion of pre-inflammatory and anti-inflammatory factors were detected. Correlations between miR-146a and these factors were also analyzed. Results: Compared with healthy control, expression levels of miR-146a in inactive and active groups were significant higher, with the highest level in active group. The expression of miR-146a and the RA severity, T helper 17 (Th17) cell ratio, RORc expression, IL-17 level showed a significant positive correlation, while it showed a significantly negative correlation with Treg cell ration, FOXP3 expression, and TGF-β1 secretion. Conclusions: These results suggested that miR-146a may be used as a disease progression marker in the peripheral blood of elder RA patients.

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Section: Introductionmentioning

confidence: 99%

Upregulated miR-146a Expression in Peripheral Blood Relates to Th17 and Treg Imbalance in Elder Rheumatoid Arthritis Patients

et al. 2022

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“…Furthermore, circulating exosomal miRNAs have been proposed as predictive and prognostic biomarkers in cancer [41,42,58]. In the context of pancreatic cancer, multiple functional analyses have confirmed the significant role that exosomal miR-NAs play in tumour cells-CAFs crosstalk, PDAC pathogenesis, diagnosis, and response to therapy [11,12,43,81,100,117]. Pancreatic cancer is highly metastatic, with liver the most common site of distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

The role of microRNAs in the modulation of cancer-associated fibroblasts activity during pancreatic cancer pathogenesis

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is the deadliest of the common cancers. A major hallmark of PDAC is an abundant and dense fibrotic stroma, the result of a disproportionate deposition of extracellular matrix (ECM) proteins. Cancer-associated fibroblasts (CAFs) are the main mediators of PDAC desmoplasia. CAFs represent a heterogenous group of activated fibroblasts with different origins and activation mechanisms. microRNAs (miRNAs) are small non-coding RNAs with critical activity during tumour development and resistance to chemotherapy. Increasing evidence has revealed that miRNAs play a relevant role in the differentiation of normal fibroblasts into CAFs in PDAC. In this review, we discuss recent findings on the role of miRNAs in the activation of CAFs during the progression of PDAC and its response to therapy, as well as the potential role that PDAC-derived exosomal miRNAs may play in the activation of hepatic stellate cells (HSCs) and formation of liver metastasis. Since targeting of CAF activation may be a viable strategy for PDAC therapy, and miRNAs have emerged as potential therapeutic targets, understanding the biology underpinning miRNA-mediated tumour cell-CAF interactions is an important component in guiding rational approaches to treating this deadly disease.

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“…In our current study, we showed that the expression levels of miR-155 were significantly increased, when PDAC cells were exposed to NiCl2 compared with the control Panc-1 and MiaPaCa-2 cells. A recent study has also mentioned that numerous exosomal miRs such as miR-155, could be potential biomarkers for the early diagnosis of this malignancy [ 109 ], while further studies have shown that miR-155 is linked to clinical stage and lymph node metastasis in PDAC patients [ 110 , 111 , 112 ].…”

Section: Discussionmentioning

confidence: 99%

Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs

Mortoglou

Manić

Djordjevic

et al. 2022

Toxics

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increasing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis.

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Exosomal microRNA in Pancreatic Cancer Diagnosis, Prognosis, and Treatment: From Bench to Bedside

Cited by 27 publications

References 190 publications

Upregulated miR-146a Expression in Peripheral Blood Relates to Th17 and Treg Imbalance in Elder Rheumatoid Arthritis Patients

Upregulated miR-146a Expression in Peripheral Blood Relates to Th17 and Treg Imbalance in Elder Rheumatoid Arthritis Patients

The role of microRNAs in the modulation of cancer-associated fibroblasts activity during pancreatic cancer pathogenesis

Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs

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