MicroRNA co-expression networks exhibit increased complexity in pancreatic ductal compared to Vater's papilla adenocarcinoma

Mazza, Tommaso; Copetti, Massimiliano; Capocefalo, Daniele; Fusilli, Caterina; Biagini, Tommaso; Carella, Massimo; Bonis, Antonio De; Mastrodonato, Nicola; Piepoli, Ada; Pazienza, Valerio; Maiello, Evaristo; Mola, Fabio F. di; Sebastiano, Pierluigi di; Andriulli, Angelo; Tavano, Francesca

doi:10.18632/oncotarget.22184

Cited by 9 publications

(10 citation statements)

References 98 publications

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“…Interestingly, miR-323a-3p was also reported as over-expressed in pancreatic ampullary tumors and found to participate in interaction networks, modulating gene expression including KRAS , with roles in axon guidance pathway [60]. Results from this and our study suggest alternative miRNA regulatory networks modulating similar pathways in AMP cancers.…”

Section: Discussionsupporting

confidence: 54%

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MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma

et al. 2019

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Despite progress in treatment strategies, only ~24% of pancreatic ductal adenocarcinoma (PDAC) patients survive >1 year. Our goal was to elucidate deregulated pathways modulated by microRNAs (miRNAs) in PDAC and Vater ampulla (AMP) cancers. Global miRNA expression was identified in 19 PDAC, 6 AMP and 25 paired, histologically normal pancreatic tissues using the GeneChip 4.0 miRNA arrays. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated pathways. Target gene expression was validated in 178 pancreatic cancer and 4 pancreatic normal tissues from The Cancer Genome Atlas (TCGA). 20 miRNAs were significantly deregulated (FC≥2 and p <0.05) (15 down- and 5 up-regulated) in PDAC. miR-216 family (miR-216a-3p, miR-216a-5p, miR-216b-3p and miR-216b-5p) was consistently down-regulated in PDAC. miRNA-modulated pathways are associated with innate and adaptive immune system responses in PDAC. AMP cancers showed 8 down- and 1 up-regulated miRNAs (FDR p <0.05). Most enriched pathways ( p <0.01) were RAS and Nerve Growth Factor signaling. PDAC and AMP display different global miRNA expression profiles and miRNA regulated networks/tumorigenesis pathways. The immune response was enriched in PDAC, suggesting the existence of immune checkpoint pathways more relevant to PDAC than AMP.

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Section: Discussionsupporting

confidence: 54%

“…Previous studies compared global miRNA expression profiles in PDAC and AMP and showed that miRNA expression profiles are distinct between PDAC and AMP tumors [16–20].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma

et al. 2019

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“…Some of these proteins have been confirmed to play key roles in cancer pathogenesis [7, 19]. Although some studies have revealed that many circRNAs act as regulators in the development of PDAC [20, 21], the actual circRNAs involved and their functions remain unclear. According to previous studies, noncoding RNAs regulate gene expression via two main ways: cis-acting and transacting regulation.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circRNA_0007334 is Predicted to Promote MMP7 and COL1A1 Expression by Functioning as a miRNA Sponge in Pancreatic Ductal Adenocarcinoma

Yang

Cong

Ren

et al. 2019

Journal of Oncology

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Pancreatic cancer remains one of the leading causes of cancer-related deaths worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor. Many circular RNAs (circRNAs) have proven to play vital roles in the physiological and pathological processes of tumorigenesis; however, their biogenesis in PDAC remains unclear. In this study, the expression profiles of circRNAs from 10 PDAC tissues and their paired adjacent nontumor tissues were analyzed through RNA sequencing analysis. An enrichment analysis was employed to predict the functions of the differentially expressed circRNAs. Sequence alignment information and mRNA microarray projects were used to predict the RNA regulatory network. The knockdown of circRNAs by small interfering RNAs followed by wound healing and western blot assays was used to confirm their functions in a PDAC cell line. A total of 278 circRNAs were identified as differentially expressed in PDAC tissue. Of these, we found that hsa_circRNA_0007334 was significantly upregulated and may serve as a competing endogenous RNA to regulate matrix metallopeptidase 7 (MMP7) and collagen type I alpha 1 chain (COL1A1) by the competitive adsorption of hsa-miR-144-3p and hsa-miR-577 to enhance the expression and functions of MMP7 and COL1A1 in PDAC. In vitro experiments confirmed these results. The present study is the first to propose two regulatory pathways in PDAC: hsa_circRNA_0007334–hsa-miR-144-3p–MMP7 and hsa_circRNA_0007334–hsa-miR-577–COL1A1.

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“…miR-339-3p was found to be deregulated in Vater’s papilla adenocarcinoma [ 38 ]. In addition, miR-339-3p was downregulated in colorectal cancer (CRC) and its low-level expression was associated with lymph node metastasis in patients with CRC [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

Nguyen

Schilling

Dobiasch

et al. 2020

Cancers

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Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice.

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MicroRNA co-expression networks exhibit increased complexity in pancreatic ductal compared to Vater's papilla adenocarcinoma

Cited by 9 publications

References 98 publications

MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma

MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma

Circular RNA hsa_circRNA_0007334 is Predicted to Promote MMP7 and COL1A1 Expression by Functioning as a miRNA Sponge in Pancreatic Ductal Adenocarcinoma

The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

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