Using microRNA Networks to Understand Cancer

Dragomir, Mihnea P.; Mafra, Ana Carolina Paschoalini; Dias, Sandra Martha Gomes; Vasilescu, C

doi:10.3390/ijms19071871

Cited by 79 publications

(67 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 It is well documented that miRNAs are aberrantly expressed and participate in the pathogenesis of various human disorders, including cancer. [10][11][12] The dysregulation of miRNAs has been detected in nearly all human cancer types, and may play either tumor-suppressive or oncogenic roles, which mainly depend on the characteristics of their target genes. [13][14][15] Many miRNAs have previously been reported to be downregulated or upregulated in PDAC, and their deregulation is involved in the control of cancerrelated biological behaviors, including cell proliferation, cell cycle distribution, apoptosis, metastasis, and resistance to radiotherapy and chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

<p>MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1</p>

Chen

Lan

et al. 2020

OTT

View full text Add to dashboard Cite

Purpose: MicroRNA-769-5p (miR-769) is aberrantly expressed and plays crucial roles in non-small cell lung cancer and melanoma. However, the expression pattern, biological role, and mechanisms of action of miR-769 in pancreatic ductal adenocarcinoma (PDAC) are yet to be fully elucidated. Therefore, we attempted to determine the potential regulatory function of miR-769 in PDAC progression and to explore the underlying mechanisms in detail. Methods: In this study, reverse-transcription quantitative polymerase chain reaction was carried out to determine the expression profile of miR-769 in PDAC. A series of experiments, including a Cell Counting Kit-8 assay, flow-cytometric analysis, Transwell migration and invasion assays, and a xenograft animal model, were applied to test whether miR-769 affects the malignancy of PDAC. Results: We found that miR-769 was significantly underexpressed in PDAC tissues and cell lines. The low miR-769 expression significantly correlated with the TNM stage and lymph node metastasis. Patients with PDAC harboring low miR-769 expression showed shorter overall survival than did the patients with high miR-769 expression. Forced upregulation of miR-769 suppressed PDAC cell proliferation, migration, and invasion in vitro; promoted apoptosis in vitro; and hindered tumor growth in vivo. Experiments on the mechanism identified ETS proto-oncogene 1 (ETS1) as a direct target gene of miR-769 in PDAC cells. Furthermore, ETS1 turned out to be upregulated in PDAC tissue samples, and the upregulation of ETS1 negatively correlated with miR-769 expression. Moreover, ETS1 knockdown simulated the tumorsuppressive effects of miR-769 overexpression on PDAC cells. Besides, ETS1 reintroduction attenuated the antitumor actions of miR-769 upregulation in PDAC cells. Conclusion: Our findings indicate that miR-769 performs tumor-suppressive functions in PDAC by directly targeting ETS1, and this miRNA may represent a potential therapeutic target for the development of anticancer therapies.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1</p>

Chen

Lan

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…miRNAs negatively modulate gene expression through direct binding to the 3-untranslated regions (3'-UTRs) of target genes, thus leading to translational inhibition and/or mRNA degradation (9). miRNAs not only serve crucial roles in regulating various fundamental cellular processes but are also closely associated with tumorigenesis and tumor development (10,11). Previous studies have reported that miRNAs are aberrantly expressed in almost all types of human cancer, including PTC (12), colorectal cancer (13), lung cancer (14), glioblastoma (15) MicroRNA-766 inhibits papillary thyroid cancer progression by directly targeting insulin receptor substrate 2 and regulating the PI3K/Akt pathway and bladder cancer (16).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑766 inhibits papillary thyroid cancer progression by directly targeting insulin receptor substrate 2 and regulating the PI3K/Akt pathway

Zhao

Chen

et al. 2018

Int J Oncol

View full text Add to dashboard Cite

MicroRNAs (miRNAs/miRs) are widely dysregulated in papillary thyroid cancer (PTC). Dysregulated miRNAs, together with their target genes, comprise a complex network that has been implicated in the regulation of PTC pathogenesis. Further knowledge of the functional roles of aberrantly expressed miRNAs in PTC, and the underlying molecular mechanisms, may assist in the identification of novel therapeutic targets. miR-766 has been well studied in human cancer; however, the expression status, specific roles and regulatory mechanisms of miR-766 in PTC remain unclear. The present study aimed to detect miR-766 expression in PTC tissues and cell lines, to explore the biological roles of miR-766 in the malignant biological behaviors of PTC cells, and to determine the underlying mechanism of action of miR-766 in PTC cells. The results revealed that miR-766 was downregulated in PTC tissues and cell lines, and its downregulation was strongly associated with TNM stage and lymph node metastasis. Overexpression of miR-766 inhibited PTC cell proliferation, colony formation, migration and invasion, promoted cell apoptosis and reduced tumor growth in vivo. Mechanistically, insulin receptor substrate 2 (IRS2) was identified as a direct target of miR-766 in PTC cells. IRS2 was upregulated in PTC tissues, and this was inversely correlated with miR-766 expression. Inhibition of IRS2 simulated the tumor suppressor activity of miR-766 in PTC cells. Restoration of IRS2 expression negated the tumor-suppressing effects of miR-766 overexpression on PTC cells. Notably, miR-766 directly targeted IRS2 to inhibit activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway in PTC cells in vitro and in vivo. Overall, these findings indicated that miR-766 may inhibit the malignant biological behaviors of PTC cells by directly targeting IRS2 and regulating the PI3K/Akt pathway, thus suggesting that this miRNA may be a promising therapeutic target for PTC.

show abstract

“…Zhu et al (31) demonstrated that Sulfatase 2 (SuLF2) could enhance cell proliferation, invasion, mobility and adhesion, and suppress apoptosis of BCa cells, which suggests that SuLF2 may be a therapeutic target for BCa treatment. Over the past decades, a number of studies have reported important roles of miRNAs in numerous types of human cancer (32)(33)(34). In addition, miRNAs have been described as functional molecules during the progression of various types of malignancy, including BCa (35).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑505 promotes cell proliferation, migration and invasion, and predicts poor prognosis in breast cancer

Wang

2019

Oncol Lett

View full text Add to dashboard Cite

microRNAs are involved in the tumor progression of various cancer types. The present study aimed to determine the prognostic significance of microRNA-505 (miR-505) in patients with breast cancer and investigate the functional role of miR-505 in BCa progression. The expression of miR-505 was estimated using reverse transcription-quantitative polymerase chain reaction. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-505 in patients with BCa. Cell experiments were performed to assess the biological function of miR-505 during BCa progression. A significant downregulated expression level of miR-505 was observed in BCa tissues and cells compared with the corresponding controls (P<0.001). The expression of miR-505 was significantly associated with distant metastasis status (P= 0.013) and Tumor-Node-Metastasis staging (P= 0.002). Furthermore, the overall survival time was significantly shorter for patients with low miR-505 expression compared with those with high miR-505 expression (P<0.001). In addition, miR-505 was identified as an independent prognostic factor for BCa. The results of cell experiments revealed that an overexpression of miR-505 could significantly inhibit BCa cell proliferation, migration and invasion, whereas a downregulation of miR-505 significantly enhanced BCa cell proliferation, migration and invasion (P<0.05). In summary, all data indicated that a low miR-505 expression level is associated with a poor prognosis for patients with BCa and promotes tumor cell proliferation, migration and invasion. Therefore, the aberrant expression of miR-505 may serve as a therapeutic target for BCa.

show abstract

Using microRNA Networks to Understand Cancer

Cited by 79 publications

References 88 publications

<p>MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1</p>

<p>MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1</p>

MicroRNA‑766 inhibits papillary thyroid cancer progression by directly targeting insulin receptor substrate 2 and regulating the PI3K/Akt pathway

Downregulation of miR‑505 promotes cell proliferation, migration and invasion, and predicts poor prognosis in breast cancer

Contact Info

Product

Resources

About