MicroRNA-365a-3p inhibits c-Rel-mediated NF-κB signaling and the progression of pancreatic cancer

Yin, Libo; Xiao, Xi; Georgikou, Christina; Yin, Yanping; Liu, Li; Karakhanova, Svetlana; Luo, Yiqiao; Gladkich, Jury; Fellenberg, Jörg; Sticht, Carsten; Gretz, Norbert; Groß, Wolfgang; Herr, Ingrid

doi:10.1016/j.canlet.2019.03.025

Cited by 32 publications

(32 citation statements)

References 34 publications

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“…Finally, we found that a higher level of miR-365a-3p in pre-operative plasma might predict the longer survival of PDAC patients following curative radical resection. To support our observation, reports of Yin et al note an association between low expression of miR-356a-3p and PDAC progression by in vitro, in vivo, and patient tissue studies [33]. Increased expression of miR-365a-3p inhibits NF-κB activity by downregulating c-Rel and thus reduced the viability of PDAC cells and induced apoptosis.…”

Section: Discussionsupporting

confidence: 87%

Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection

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et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive cancers with a less than 6% five-year survival rate. Circulating microRNAs (miRNAs) are emerging as a useful tool for non-invasive diagnosis and prognosis estimation in the various cancer types, including PDAC. Our study aimed to evaluate whether miRNAs in the pre-operative blood plasma specimen have the potential to predict the prognosis of PDAC patients. In total, 112 PDAC patients planned for surgical resection were enrolled in our prospective study. To identify prognostic miRNAs, we used small RNA sequencing in 24 plasma samples of PDAC patients with poor prognosis (overall survival (OS) < 16 months) and 24 plasma samples of PDAC patients with a good prognosis (OS > 20 months). qPCR validation of selected miRNA candidates was performed in the independent cohort of PDAC patients (n = 64). In the discovery phase of the study, we identified 44 miRNAs with significantly different levels in the plasma samples of the group of good and poor prognosis patients. Among these miRNAs, 23 showed lower levels, and 21 showed higher levels in plasma specimens from PDAC patients with poor prognosis. Eleven miRNAs were selected for the validation, but only miR-99a-5p and miR-365a-3p were confirmed to have significantly lower levels and miR-200c-3p higher levels in plasma samples of poor prognosis cases. Using the combination of these 3-miRNA levels, we were able to identify the patients with poor prognosis with sensitivity 85% and specificity 80% (Area Under the Curve = 0.890). Overall, 3-miRNA prognostic score associated with OS was identified in the pre-operative blood plasma samples of PDAC patients undergoing surgical resection. Following further independent validations, the detection of these miRNA may enable identification of PDAC patients who have no survival benefit from the surgical treatment, which is associated with the high morbidity rates.

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Section: Discussionsupporting

confidence: 87%

Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection

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et al. 2020

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“…11 miR-365a-3p was reported to have a tumor-suppressive role in pancreatic cancer but an oncogenic role in laryngeal squamous cell carcinoma. 12,13 For instance, miR-365a-3p was found to decrease expression in pancreatic cancer tissues and regulates c-Rel to inhibit cancer progression. 12 On the contrary, miR-365a-3p was found elevated expression in laryngeal squamous cell carcinoma, and the knockdown of miR-365a-3p could suppress cell growth, metastasis through regulating PI3K/AKT signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 For instance, miR-365a-3p was found to decrease expression in pancreatic cancer tissues and regulates c-Rel to inhibit cancer progression. 12 On the contrary, miR-365a-3p was found elevated expression in laryngeal squamous cell carcinoma, and the knockdown of miR-365a-3p could suppress cell growth, metastasis through regulating PI3K/AKT signaling pathway. 13 These results implied the importance of miR-365-3p in regulating cancer progression.…”

Section: Introductionmentioning

confidence: 99%

<p>Long Non-Coding RNA NEAT1 Serves as Sponge for miR-365a-3p to Promote Gastric Cancer Progression via Regulating ABCC4</p>

Gao

Liu

Zhang

et al. 2020

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Long non-coding RNA (lncRNA) was reported to be a crucial regulator in cancer. In this work, our purpose is to explore the biological roles of nuclear paraspeckle assembly transcript 1 (NEAT1) in gastric cancer (GC). Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect NEAT1 expression in GC cells and normal cells. GC cell behaviors after NEAT1 overexpression or downregulation were analyzed by Cell Counting Kit-8 assay, colony formation assay, woundhealing assay, and flow cytometry assay. Bioinformatic tools were used to analyze the significance of NEAT1 in GC. The involvement of microRNA-365a-3p (miR-365a-3p) and ATP-binding cassette subfamily C member 4 (ABCC4) in the biological roles of NEAT1 in GC progression was validated by luciferase activity reporter assay and rescue experiments. Results: We found NEAT1 increased expression in both GC tissues and cells and correlated with poorer overall survival of cancer patients. We found NEAT1 overexpression promotes, while its knockdown inhibits GC cell proliferation, colony formation, invasion, and cell cycle progression in vitro. Mechanism analyses showed that NEAT1 serves as a ceRNA to upregulate ABCC4 expression via sponging miR-365a-3p. Conclusion: In this study, we revealed a NEAT1/miR-365a-3p/ABCC4 triplet in GC progression, which may provide novel targeted therapy markers for GC.

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“…sites, we identified 309 target genes that are individually or commonly regulated by the three miRNA candi network plot ( Figure 7A). To follow up on our previous studies showing that sulforaphane normalizes enh miRNA signaling [8,23], several candidate genes were identified ( Figure 7B, Table S4). The top candidate was predicted to regulate the highest number of NF-κB-related target genes, followed by miR27b-5p and miR2 overlapped in regulation of NF-κB-related target genes.…”

Section: Sulforaphane Sf102 and Sf134 Induce Differential Microrna Ementioning

confidence: 99%

“…Sulforaphane is one of the best studied bioactive anti-inflammatory agents and suggested to induce detoxifying enzymes, cell cycle arrest, apoptosis and epigenetic regulation [6]. In pancreatic cancer, sulforaphane normalized increased NF-κB signaling in tumor stem cells by the induction of miRNA-365 expression, which inhibited the expression of the NF-κB subunit c-Rel by binding to its 3´-UTR [8,9].…”

Section: Introductionmentioning

confidence: 99%

Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects

et al. 2020

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The naturally occurring isothiocyanate sulforaphane, found in Brassicaceae vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-κB-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group (S(O)) to either sulfimidoyl (S(NR)) or sulfonimidoyl (S (O) (NR)) groups, and characterized them in the cell lines of pancreatic cancer and several other tumor entities, including the NCI-60 cell panel. MTT and colony forming assays, flow cytometry, immunohistochemistry, microRNA arrays, bioinformatics, tumor xenotransplantation, and Kaplan Meier survival curves were performed. Compared to sulforaphane, the analogue SF102 was most efficient in inhibition of viability, colony formation, tumor growth, and the induction of apoptosis, followed by SF134. Side effects were not observed, as concluded from the body weight and liver histology of chick embryos and survival of C. elegans nematodes. Among 6659 differentially regulated microRNAs, miR29b-1-5p, and miR-27b-5p were downregulated by sulforaphane compared to controls, but upregulated by SF102 and SF134 compared to sulforaphane, suggesting differential signaling. Each substance was involved in the regulation of several NF-κB-related target genes. In conclusion, sulforaphane analogues are promising for the development of highly active new drugs in cancer treatment.

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MicroRNA-365a-3p inhibits c-Rel-mediated NF-κB signaling and the progression of pancreatic cancer

Cited by 32 publications

References 34 publications

Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection

Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection

<p>Long Non-Coding RNA NEAT1 Serves as Sponge for miR-365a-3p to Promote Gastric Cancer Progression via Regulating ABCC4</p>

Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects

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