Identification of potential microRNA panels for pancreatic cancer diagnosis using microarray datasets and bioinformatics methods

Shams, Roshanak; Saberi, Samaneh; Mr, Zali; Sadeghi, Amir; Ghafouri‐Fard, Soudeh; Aghdaei, Hamid Asadzadeh

doi:10.1038/s41598-020-64569-1

Cited by 42 publications

(35 citation statements)

References 42 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For miR-6746, it has been shown to have specific expression level in the plasma of pancreatic cancer patients but not in those of other patients ( Sheng et al, 2020 ). For miR-8073, it has been identified in both pancreatic ( Shams et al, 2020 ) and breast ( Cui et al, 2018 ) cancers, implying that such microRNA may distinguish two cancer subtypes from the other cancer subtypes and normal controls.…”

Section: Resultsmentioning

confidence: 99%

Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes

Yuan

Chen

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

Cancer is one of the most threatening diseases to humans. It can invade multiple significant organs, including lung, liver, stomach, pancreas, and even brain. The identification of cancer biomarkers is one of the most significant components of cancer studies as the foundation of clinical cancer diagnosis and related drug development. During the large-scale screening for cancer prevention and early diagnosis, obtaining cancer-related tissues is impossible. Thus, the identification of cancer-associated circulating biomarkers from liquid biopsy targeting has been proposed and has become the most important direction for research on clinical cancer diagnosis. Here, we analyzed pan-cancer extracellular microRNA profiles by using multiple machine-learning models. The extracellular microRNA profiles on 11 cancer types and non-cancer were first analyzed by Boruta to extract important microRNAs. Selected microRNAs were then evaluated by the Max-Relevance and Min-Redundancy feature selection method, resulting in a feature list, which were fed into the incremental feature selection method to identify candidate circulating extracellular microRNA for cancer recognition and classification. A series of quantitative classification rules was also established for such cancer classification, thereby providing a solid research foundation for further biomarker exploration and functional analyses of tumorigenesis at the level of circulating extracellular microRNA.

show abstract

Section: Resultsmentioning

confidence: 99%

Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes

Yuan

Chen

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…miR-23a-3p, miR-126-3p, miR-146a-5p, and miR-5100 were identified as some of the most abundant miRNAs in the temporal lobe neocortex of human brain [ 62 ]. Although the role of miR-5100 remains elusive, it has been identified as a disease biomarker for cancer [ 65 ] and lupus [ 66 ]. miR-23 is involved in neuronal specification, and miR-146a implicated in the prevention of neuroligin 1-dependent synaptogenesis, and both were enriched in astrocytes compared to neurons [ 54 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Differential RNA packaging into small extracellular vesicles by neurons and astrocytes

et al. 2021

View full text Add to dashboard Cite

Background Small extracellular vesicles (sEVs) mediate intercellular communication by transferring RNA, proteins, and lipids to recipient cells. These cargo molecules are selectively loaded into sEVs and mirror the physiological state of the donor cells. Given that sEVs can cross the blood–brain barrier and their composition can change in neurological disorders, the molecular signatures of sEVs in circulation can be potential disease biomarkers. Characterizing the molecular composition of sEVs from different cell types is an important first step in determining which donor cells contribute to the circulating sEVs. Methods Cell culture supernatants from primary mouse cortical neurons and astrocytes were used to purify sEVs by differential ultracentrifugation and sEVs were characterized using nanoparticle tracking analysis, transmission electron microscopy and western blot. RNA sequencing was used to determine differential expression and loading patterns of miRNAs in sEVs released by primary neurons and astrocytes. Motif analysis was conducted on enriched miRNAs in sEVs and their respective donor cells. Results Sequencing total cellular RNA, and miRNAs from sEVs isolated from culture media of postnatal mouse cortical neurons and astrocytes revealed a distinct profile between sEVs and their corresponding cells. Though the total number of detected miRNAs in astrocytes was greater than neurons, neurons expressed more sEV-associated miRNAs than astrocytes. Only 20.7% of astrocytic miRNAs were loaded into sEVs, while 41.0% of neuronal miRNAs were loaded into sEVs, suggesting differences in the cellular sorting mechanisms. We identified short RNA sequence motifs, or EXOmotifs, on the miRNAs that were differentially loaded or excluded from sEVs. A sequence motif GUAC was enriched in astrocytic sEVs. miRNAs preferably retained in neurons or astrocytes had a similar RNA motif CACACA, suggesting a cell-type-independent mechanism to maintain cellular miRNAs. mRNAs of five RNA-binding proteins associated with passive or active RNA sorting into sEVs were differentially expressed between neurons and astrocytes, one of which, major vault protein was higher in astrocytes than in neurons and detected in astrocytic sEVs. Conclusions Our studies suggest differences in RNA sorting into sEVs. These differences in miRNA signatures can be used for determining the cellular sources of sEVs altered in neurological disorders.

show abstract

“…Metastasis is a key factor influencing the prognosis of PC, and it is well-known that miRNAs can regulate the development, progression and metastasis of breast cancer (33,34). In PC, miRNAs have been found to affect tumor metastasis and function as biomarkers, and prognostic and therapeutic modulators of PC (35)(36)(37)(38). For example, miR-141 was associated with the growth and metastasis of PC, whereas miR203a-3p inhibited PC cell growth, proliferation, epithelia-mesenchymal transition and apoptosis (39).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways

et al. 2020

View full text Add to dashboard Cite

MicroRNA (miR)-23b-3p plays an important role in tumor growth, proliferation, invasion and migration in pancreatic cancer (PC). However, the function and mechanistic role of miR-23b-3p in the development of PC remains largely unknown. In the present study, the miR-23b-3p levels in the serum of patients with PC were found to be elevated, and the phosphorylation levels of Janus kinase (JAK)2, PI3K, Akt and NF-κВ were found to be upregulated. In addition, miR-23b-3p was induced in response to interleukin-6 (IL-6), which is known to be involved in the progression of PC. Overexpression of miR-23b-3p, on the other hand, activated the JAK/PI3K and Akt/NF-κB signaling pathways in PC cells, as evidenced by miR-23b-3p-induced upregulation of phosphorylated (p-) JAK2, p-PI3K, p-Akt and p-NF-κВ, as well as the downregulation of PTEN; and these effects were found to be reversible by miR-23b-3p inhibition. Furthermore, miR-23b-3p was found to downregulate PTEN by directly targeting the 3'-untranslated region of PTEN mRNA. Notably, in an in vivo xenograft mouse model, overexpression of miR-23b-3p accelerated PC cell-derived tumor growth, activated the JAK/Akt/NF-κВ signaling pathway and promoted liver metastasis. In contrast, knockdown of miR-23b-3p suppressed tumor growth and metastasis as well as JAK/Akt/NF-κВ signaling activity. In vivo imaging of the mice further confirmed the metastasis promoting role of miR-23b-3p in PC. These results suggested that miR-23b-3p enhances PC cell tumorigenesis and metastasis, at least, partially via the JAK/PI3K and Akt/NF-κB signaling pathways. Therefore, targeting miR-23b-3p or the JAK/PI3K and Akt/NF-κB signalings may be potential therapeutic strategy against PC.

show abstract

Identification of potential microRNA panels for pancreatic cancer diagnosis using microarray datasets and bioinformatics methods

Cited by 42 publications

References 42 publications

Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes

Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes

Differential RNA packaging into small extracellular vesicles by neurons and astrocytes

MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways

Contact Info

Product

Resources

About

Identification of potential microRNA panels for pancreatic cancer diagnosis using microarray datasets and bioinformatics methods

Cited by 42 publications

References 42 publications

Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes

Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes

Differential RNA packaging into small extracellular vesicles by neurons and astrocytes

MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑&kappa;B signaling pathways

Contact Info

Product

Resources

About

MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways