MicroRNAs as Potential Targets for Therapeutic Intervention With Metastasis of Non-small Cell Lung Cancer

Weidle, Ulrich H.; Birzele, Fabian; Nopora, Adam

doi:10.21873/cgp.20116

Cited by 55 publications

(43 citation statements)

References 175 publications

(257 reference statements)

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“…Multiple miRNAs have been identi ed as potential diagnostic biomarkers and therapeutic targets for NSCLC. For example, expression of miR-128-3p was signi cantly up-regulated in NSCLC tissues by comparison with adjacent normal tissues; its overexpression remarkably induced the migration and invasion of A549, Calu-3 and H520 cells [17]. In the present research, miR-199a-5p was found to be dramatically down-regulated in NSCLC tissues, serum samples of NSCLC patients and multiple NSCLC cell lines.…”

Section: Discussionsupporting

confidence: 52%

MiR-199a-5p-HIF-1α-STAT3 positive feed-back loop contributes to the progression of NSCLC

Yang

Zheng

Tan

et al. 2020

Preprint

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Background Non-small cell lung cancer (NSCLC), is the most common malignancy worldwide. MiR-199a-5p has been reported to play important roles in multiple tumors, inclusive of NSCLC. Whereas, little is definitively known pertaining to its explicit mechanism of action in NSCLC. Methods Expression of miR-199a-5p and HIF-1α mRNA were quantified employing qRT-PCR. H1299 and A549 cells were transiently transfected with miR-199a-5p mimics or inhibitors. Then CCK-8 assays, flow cytometry analysis, Transwell assay were implemented for detecting cell proliferation, cell cycle, apoptosis, migration and invasion of NSCLC cells, respectively. HIF-1α, STAT3 and p-STAT3 expression were detected via Western blotting. Bioinformatic analysis and dual-luciferase assay were performed for monitoring interaction between miR-199a-5p, HIF-1α and STAT3. Xenograft models were established with nude mice for further analyzing Bevacizumab resistance of NSCLC. Results MiR-199a-5p expression was markedly attenuated in NSCLC tissues and cell lines. Overexpression of miR-199a-5p constrained proliferation, migration, invasion but induced apoptosis of NSCLC cells. HIF-1α was identified as a direct target of miR-199a-5p. Further study confirmed a positive feed-back loop between miR-199a-5p, HIF-1α and STAT3. Co-transfection of HIF-1α or STAT3 overexpression plasmids counteracted effects of miR-199a-5p. Further study substantiated that feed-back loop might be in association with the Bevacizumab resistance of NSCLC cells . Conclusion MiR-199a-5p constrained the progression and Bevacizumab resistance of NSCLC by suppressing HIF-1α and STAT3, while HIF-1α/STAT3 axis suppressed the expression of miR-199a-5p, which forms a positive feed-back loop to promote the sustaining progression of NSCLC.

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Section: Discussionsupporting

confidence: 52%

MiR-199a-5p-HIF-1α-STAT3 positive feed-back loop contributes to the progression of NSCLC

Yang

Zheng

Tan

et al. 2020

Preprint

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“…In recent years, with the development of molecular biology and the rise of translational medicine, novel markers and technologies are emerging for diagnosis and treatment of LUAC. [4][5][6] Circular RNAs (circRNAs) are categorized as a type of endogenous non-coding RNAs (ncRNAs) and have been regarded as transcription errors during the splicing process. Recently, accumulating evidences have revealed that circRNAs, which formed a covalent closed continuous loop without a polyadenylated tail and 5ʹ to 3ʹ polarity, are of vital significance in various cellular processions, like gene expression regulation, cell cycle progression, chromatin modification, etc.…”

Section: Introductionmentioning

confidence: 99%

<p>Identification of circRNA-miRNA-mRNA Networks for Exploring the Fundamental Mechanism in Lung Adenocarcinoma</p>

Liang¹,

Zhang²,

Zhang³

et al. 2020

OTT

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Background: Circular RNAs (circRNAs) were elucidated to act as competing endogenous RNAs (ceRNAs) and to play significant roles in cancer initiation and progression. We aimed to identify the important circRNAs in lung adenocarcinoma and intended to predict the functions of them via the bioinformatics analysis. Methods: We extracted data from three Gene Expression Omnibus (GEO) datasets, GSE101586, GSE101684, and GSE104854, and identified the common differentially expressed circRNAs. Agarose gel electrophoresis and Sanger sequencing were used to verify these significant circRNAs. Then, qRT-PCR was performed to validate the expression through matched tissues and cell lines. Afterwards, a ceRNA network was constructed and functional analysis was performed to predict the potential mechanisms of circRNAs. Results: Five circRNAs (hsa_circ_0072088, hsa_circ_0082564, hsa_circ_0008274, hsa_-circ_0000519 and hsa_circ_0003528) were identified differentially expressed in the three datasets. Following the Agarose gel electrophoresis and qRT-PCR validation, hsa_circ_0072088 and hsa_-circ_0008274 were chosen for further analysis. A ceRNA network of hsa_circ_0072088 and hsa_circ_0008274 was built based on the CSCD/TargetScan/MiRTarbase/StarBase 3.0. Then, the functional analysis showed that several meaningful terms were identified, such as "epithelial to mesenchymal transition (EMT)", "Cellular response to TGF-β stimulus", "MAPK signaling pathway", and "PI3K-AKT signaling pathway". Finally, several significant circRNA/miRNA/mRNA regulatory axes, which were predicted relating to cancer progress, were noted from the network. Conclusion: We identified significant circRNAs and meaningful circRNA-miRNA-mRNA networks to provide novel insight into pathogenesis and therapy of lung adenocarcinoma.

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“…MicroRNAs (miRNAs/miRs) are endogenous, small, noncoding and highly conserved RNAs 11,12 . Recent studies have revealed that miRNAs are implicated in various cellular processes [13][14][15] .…”

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confidence: 99%

miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44

Zou

Zhu

Lian

et al. 2019

Sci Rep

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Lung cancer is the leading cause of cancer-related deaths worldwide, with 50-70% of patients suffering from bone metastasis. Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis. In the present study, we demonstrated that reduced miR-192-5p and increased TRIM44 levels were associated with the proliferation, migration and invasion of lung cancer. Furthermore, the potential functions of miR-192-5p were explored in A549 and NCI-H1299 cells. We found that miR-192-5p upregulation suppressed tumour behaviours in lung cancer cells. To further investigate whether miR-192-5p is associated with TRIM44, we used TargetScan software to predict the binding site between miR-192-5p and TRIM44. Luciferase activity assays were performed to verify this prediction. In addition, the significant role of miR-192-5p in negatively regulating TRIM44 expression was manifested by our research group. our results suggest that miR-192-5p inhibited the proliferation, migration and invasion of lung cancer through TRIM44.

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MicroRNAs as Potential Targets for Therapeutic Intervention With Metastasis of Non-small Cell Lung Cancer

Cited by 55 publications

References 175 publications

MiR-199a-5p-HIF-1α-STAT3 positive feed-back loop contributes to the progression of NSCLC

MiR-199a-5p-HIF-1α-STAT3 positive feed-back loop contributes to the progression of NSCLC

<p>Identification of circRNA-miRNA-mRNA Networks for Exploring the Fundamental Mechanism in Lung Adenocarcinoma</p>

miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44

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