Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

Khan, Imteyaz Ahmad; Singh, Nidhi; Rashid, Safoora; Singh, Vishwajeet; Gunjan, Deepak; Das, Prasenjit; Dash, Nihar Ranjan; Pandey, Ravindra Mohan; Chauhan, Shyam S.; Gupta, Surabhi; Saraya, Anoop

doi:10.1038/s41598-021-82266-5

Cited by 35 publications

(16 citation statements)

References 62 publications

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“…The comparative analysis of the identified miRNAs' influence on the ERα expression showed that miR-181a-2 demonstrates the maximal inhibitory activity (Figure 1a), and all following experiments were performed with the latter. The role of this miRNA in cancer progression is of great interest as its expression correlates with cell proliferation and with the survival of cancer patients [79][80][81].…”

Section: Resultsmentioning

confidence: 99%

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Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

et al. 2021

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Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.

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Section: Resultsmentioning

confidence: 99%

“…following experiments were performed with the latter. The role of this miRNA in cancer progression is of great interest as its expression correlates with cell proliferation and with the survival of cancer patients [79][80][81].…”

Section: Resultsmentioning

confidence: 99%

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

et al. 2021

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“…Many studies have reported speci c upregulation or downregulation of serum miRNAs in certain types of cancers [9,[11][12][13][14][15][16][17][18][31][32][33][34][35]. Yet, few studies have investigated the potential of serum miRNAs as a general cancer screening markers across multiple cancer subtypes [6,19].…”

Section: Discussionmentioning

confidence: 99%

Identification of Four Serum miRNAs as Potential Markers to Screen for Thirteen Cancer Types

Chen¹,

Dhahbi²

2021

Preprint

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Introduction: Cancer has consistently remained one of the top causes of death in the United States every year, with many cancer deaths preventable if detected early. Circulating serum miRNAs pose as a promising, minimally invasive supplement, or even alternative, to many current screening procedures. Many studies have shown that different serum miRNAs can discriminate healthy individuals from those with certain types of cancer. Although many of those miRNAs are often reported to be significant in one cancer type, they are also altered in other types of cancers. Currently, very few studies have investigated serum miRNA biomarkers for multiple different cancer types simultaneously for general cancer screening.Method: To identify serum miRNAs that would be useful in simultaneously screening multiple types of cancers, microarray cancer datasets were curated, yielding 13 different types of cancer with a total of 3352 cancer samples and 2809 non-cancer samples. The samples were then divided into discovery and validation sets. A hundred random forest models were built using the discovery set to select candidate miRNAs. The selected miRNAs were then used in the validation set to see how well they can differentiate cancer from normal samples in an independent dataset. Further analysis of the interactions between these miRNAs and their target mRNAs were investigated as well.Result: The random forest models achieved an average of 97% accuracy in the discovery set with 95% bootstrap confidence interval from 0.9544 to 0.9778. The selected miRNAs were hsa-miR-663a, hsa-miR-6802-5p, hsa-miR-6784-5p, hsa-miR-3184-5p, and hsa-miR-8073. Each individual miRNA exhibited high area under the curve (AUC) value using receiver operating characteristic analysis. Moreover, the combination of four out of the five miRNAs achieved the highest AUC value of 0.9815 with perfect sensitivity, indicating that these miRNAs have a high potential for cancer screening. miRNA-mRNA interaction and protein-protein interaction analysis provided insights into how these miRNAs may play a role in cancer in general.

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“…The results from this study also demonstrated that these five miRNAs had significantly different levels between the serum of patients with CP and those with earlystage PDAC. This panel has the potential to become part of a multicomponent screening panel of CP patients for PDAC [63]. One of the most promising and investigated miRNAs in PDAC is miR-21-5p, which is also overexpressed in many other types of cancer [64].…”

Section: Circulating Mirnas and Their Diagnostic Significance In Early-stage Pdacmentioning

confidence: 99%

The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient’s blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.

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Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

Cited by 35 publications

References 62 publications

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

Identification of Four Serum miRNAs as Potential Markers to Screen for Thirteen Cancer Types

The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma

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