Downregulated miR-98-5p promotes PDAC proliferation and metastasis by reversely regulating MAP4K4

Fu, Yue; Liu, Xinchun; Chen, Qiuyang; Liu, Tongtai; Lü, Cheng; Yu, Jun; Miao, Yi; Wei, Jishu

doi:10.1186/s13046-018-0807-2

Cited by 67 publications

(46 citation statements)

References 42 publications

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“…25 In addition, miR-98-5p can promote the development of pancreatic ductal adenocarcinoma by downregulating mitogen-activated protein 4 kinase 4 (MAP4K4) and inhibiting the downstream mitogen-activated protein kinase/extracellular regulated protein kinases (MAPK/ ERK) signaling pathway. 26 However, hsa-let-7a-5p, hsa-let -7b-5p and hsa-let-7c-5p play an important role in the occurrence and development of colorectal cancer, multiple myeloma and acute lymphoblastic leukemia. [27][28][29] This finding provides a theoretical basis for understanding the working mechanism of hsa_circRNA_012515 in the occurrence and development of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

<p>hsa_circRNA_012515 Is Highly Expressed in NSCLC Patients and Affects Its Prognosis</p>

Fu¹,

Huang²,

Tang³

et al. 2020

CMAR

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Background: NSCLC is one of the most common and most lethal malignancies throughout the world, and there is still a lack of sensitive diagnostic biomarkers. Identifying novel NSCLC biomarkers can help with the diagnosis and clinical decision-making. Methods: Identifying the differentially expressed circRNAs in three cases of NSCLC tissues by high-throughput circRNA microarray sequencing. qRT-PCR was employed to detect the expression levels of hsa_circRNA_012515 in 80 cases of NSCLC tissues (tumor resection patients) and 60 cases of peripheral blood samples (chemotherapy patients), NSCLC cells and gefitinibresistant NSCLC cell lines. Then combining with clinical data, we discussed whether it was feasible to use hsa_circRNA_012515 as the diagnostic and prognostic biomarker for NSCLC. Results: In the cancerous tissues from NSCLC patients, NSCLC cells and gefitinib-resistant cell lines, the average expressions of hsa_circRNA_012515 increased significantly (P<0.01). Patients of stage III-IV, with lymph node metastases, had an overexpression of hsa_circRNA_012515. High expression of hsa_circRNA_012515 was associated with lower OS and shorter PFS, and it is closely related to the prognosis of the patients. Bioinformatic analysis indicated that hsa_circRNA_012515 interacted with 5 miRNAs. This finding may shed new light on the subsequent studies on the working mechanism and functions. Conclusion: Our study showed that hsa_circRNA_012515 may be a novel biomarker candidate for NSCLC. However, further studies are needed to ascertain the working mechanism of hsa_circRNA_012515 in the occurrence and development of NSCLC.

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Section: Discussionmentioning

confidence: 99%

<p>hsa_circRNA_012515 Is Highly Expressed in NSCLC Patients and Affects Its Prognosis</p>

Fu¹,

Huang²,

Tang³

et al. 2020

CMAR

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“…Through analyzing the miRNA and mRNA expression connection in BC patients, we identi ed a novel hsa-miR-98-5p/IGF1 axis that may play a crucial role in BC. hsa-miR-98-5p has a controversial role in human cancers as it can function as either tumor suppressor or oncogene [22,23]. For example, Fu and co-workers showed that downregulation of hsa-miR-98-5p could promote the development of pancreatic ductal adenocarcinoma via inversely regulating the expression of MAP4K4, indicating the tumor suppressive role of hsa-miR-98-5p [22].…”

Section: Discussionmentioning

confidence: 99%

“…hsa-miR-98-5p has a controversial role in human cancers as it can function as either tumor suppressor or oncogene [22,23]. For example, Fu and co-workers showed that downregulation of hsa-miR-98-5p could promote the development of pancreatic ductal adenocarcinoma via inversely regulating the expression of MAP4K4, indicating the tumor suppressive role of hsa-miR-98-5p [22]. On the contrary, Wang et al showed hsa-miR-98-5p was enriched expression in epithelial ovarian cancer, and regulated the sensitive of cancer cells to cisplatin [23].…”

Section: Discussionmentioning

confidence: 99%

Identifying of a Novel miR-98-5p/IGF1 Axis Contributes the Pathogenesis of Breast Cancer Using Comprehensive Bioinformatic Analyses Methods and Experiments Validation

Sun

Luo

et al. 2020

Preprint

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Background: Breast cancer (BC) is a huge threat for the health of women worldwide. Although the numerous microRNAs (miRNA) have been identified to be aberrantly expressed in BC, the construction of a comprehensive miRNA-messenger RNA (mRNA) network is still needed. This study was aimed to identify BC-associated miRNAs through analyzing microarray datasets obtained from GEO database and to construct a miRNA-mRNA network for BC. Methods: Limma package was used to identify differentially expressed miRNAs (DEMs) in microarray datasets. Genes targeted by DEMs were analyzed with mirTarBase. Gene Ontology and pathway enrichment analysis for the predicted target genes were performed at DAVID. Correlation of DEMs and target genes was analyzed at ENCORI. Based on these results, a miRNA-mRNA regulatory network was constructed. Results: A total of 17 overlapping DEMs were identified at these two microarray datasets. Expression of DEMs in BC were further validated by ENCORI. By utilizing miRTarBase, a total of 167 target genes for DEMs were obtained. 10 hub genes (AKT1, MYC, VEGFA, CCND1, PTEN, IL6, CASP3, KRAS, IGF1, ESR1) were identified after network analysis at STRING and CytoScape. Through analyzing the effects of hub genes on overall survival of BC patients and correlation of DEMs and hub genes, we found hsa-miR-98-5p/IGF1 axis may play a crucial role in BC progression. The connections of hsa-miR-98-5p and IGF1 were further validated by luciferase activity reporter assay and functional assays. Conclusion: In this work, a miRNA-mRNA network related to BC progression was built, and identified one important miRNA-mRNA axis in BC.

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“…Interestingly, multiple miRNAs have also been found abnormally expressed in tumors and regulate their cell biological processes ( 13 ). MiR-98-5p is one member of miRNAs, and its downregulation has been shown to promote pancreatic ductal adenocarcinoma (PDAC) proliferation and metastasis ( 14 ). In addition, it is found that miR-98-5p enhances the sensitivity of epithelial OC to cisplatin ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

A Positive Feedback Loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-1α Plays a Role in the Progression of Ovarian Cancer

et al. 2020

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Background Accumulating studies have revealed that long non-coding RNA (lncRNA) and microRNA (miRNA) contribute to ovarian cancer (OC). DSCR8 has been found to mediate hepatocellular carcinoma development, while its role in OC remains to be explored. Methods In this study, lncRNA DSCR8 and miR-98-5p expressions in OC tissues and adjacent non-cancer tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Besides, gain-of-function or loss-of-function assays of DSCR8 and miR-98-5p were conducted on OC cell lines SKOV-3 and A2780. Cell proliferation was detected with Cell Counting Kit (CCK)8 and colony formation assay, and western blot was used to test the apoptotic levels of OC cells. Transwell assay was conducted to examine cell invasion, and the epithelial–mesenchymal transition (EMT) of OC cells was tested by western blot. Moreover, luciferase activity assay and RNA immunoprecipitation (RIP) assay were conducted to verify the relationships between DSCR8 and miR-98-5p, miR-98-5p, and signal transducer and activator of transcription 3 (STAT3). Results DSCR8 was remarkedly increased in OC tissues and associated with poorer survival of OC patients. Overexpressing DSCR8 promoted cell proliferation, invasion, and EMT but inhibited apoptosis. On the other hand, miR-98-5p was downregulated in OC tissues and relieved the progression of OC. Moreover, overexpressed DSCR8 increased the levels of STAT3 and hypoxia inducible factor 1 alpha (HIF-1α) and dampened the functions of miR-98-5p on OC. Pharmaceutical intervention of STAT3 and HIF-1α significantly altered the expressions of DSCR8 and miR-98-5p. Conclusion The present results suggested a positive feedback loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-α axis in the progression of OC.

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Downregulated miR-98-5p promotes PDAC proliferation and metastasis by reversely regulating MAP4K4

Cited by 67 publications

References 42 publications

<p>hsa_circRNA_012515 Is Highly Expressed in NSCLC Patients and Affects Its Prognosis</p>

<p>hsa_circRNA_012515 Is Highly Expressed in NSCLC Patients and Affects Its Prognosis</p>

Identifying of a Novel miR-98-5p/IGF1 Axis Contributes the Pathogenesis of Breast Cancer Using Comprehensive Bioinformatic Analyses Methods and Experiments Validation

A Positive Feedback Loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-1α Plays a Role in the Progression of Ovarian Cancer

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