MicroRNA‑4500 suppresses tumor progression in non‑small cell lung cancer by regulating STAT3

Li, Zhiying; Zhang, Zi‐Zhou; Bi, Hui; Zhang, Qiudi; Zhang, Sujuan; Zhou, Lin; Zhu, Xiaoqin; Zhou, Jun

doi:10.3892/mmr.2019.10737

Cited by 8 publications

(6 citation statements)

References 40 publications

(33 reference statements)

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“…In recent years, STAT3 has been found to be constitutively activated in multiple types of human cancers, indicating that STAT3 is a valuable target for cancer therapy [28]. STAT3 has been identi ed to be abnormally increased in NSCLC tissues and cell lines, and knockdown of STAT3 can induce apoptosis, reduce proliferation, migration and invasion of A549 and H1975 cells [29]. Consistently, we demonstrated that transfection of STAT3 overexpression plasmids notably induced proliferation, migration and invasion of NSCLC cells.…”

Section: Discussionsupporting

confidence: 78%

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: 78%

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, STAT3 has been found to be constitutively activated in multiple types of human cancers, indicating that STAT3 is a valuable target for cancer therapy (Furtek et al, 2016 ). STAT3 has been identified to be abnormally increased in NSCLC tissues and cell lines, and knockdown of STAT3 can induce apoptosis and reduce the proliferation, migration, and invasion of A549 and H1975 cells (Li Z. Y. et al, 2019 ). Consistently, we demonstrated that transfection of STAT3 overexpression plasmids notably induced the proliferation, migration, and invasion of NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

MiR-199a-5p–HIF-1α-STAT3 Positive Feedback Loop Contributes to the Progression of Non-Small Cell Lung Cancer

Yang

Zheng

Tan

et al. 2021

Front. Cell Dev. Biol.

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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. However, little is definitively known pertaining to its explicit mechanism of action in NSCLC.Methods: The expressions of miR-199a-5p and hypoxia-inducible factor-1α (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, and Transwell assay were performed for detecting cell proliferation, cell cycle, apoptosis, migration, and invasion of NSCLC cells, respectively. HIF-1α, signal transducer and activator of transcription 3 (STAT3), and p-STAT3 expressions were detected via Western blotting. Bioinformatic analysis and dual-luciferase assay were performed to investigate the interactions among miR-199a-5p, HIF-1α, and STAT3. Xenograft models were established with nude mice for further analyzing the bevacizumab resistance of NSCLC cells.Results: MiR-199a-5p expression was markedly attenuated in NSCLC tissues and cell lines. Overexpression of miR-199a-5p repressed the proliferation, migration, and invasion but induced the apoptosis of NSCLC cells. HIF-1α was identified as a direct target of miR-199a-5p. There was a positive feedback loop among miR-199a-5p, HIF-1α, and STAT3. Co-transfection of HIF-1α or STAT3 overexpression plasmids counteracted the effects of miR-199a-5p. In vivo experiments indicated that the feedback loop was in association with the bevacizumab resistance of NSCLC cells.Conclusion: MiR-199a-5p blocked the progression of NSCLC and sensitized NSCLC cells to bevacizumab by suppressing HIF-1α and STAT3, while the HIF-1α/STAT3 axis suppressed the expression of miR-199a-5p, which forms a positive feedback loop to promote the sustaining progression of NSCLC.

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“…Other reports have illustrated that RHPN2 activates the STAT3 pathway and expedites the progression of ovarian cancer, and the use of the STAT3 inhibitors signally eases the malignant cell behaviors induced by RHPN2 [ 52 ]. More importantly, STAT3 activation induces a poor prognosis for NSCLC, and inhibition of STAT3 has great potential for treating NSCLC [ 53 , 54 ]. Additionally, AK027294 enhances the growth of NSCLC by up-regulating STAT3 [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis

Zhao

Jin

et al. 2022

Bioengineered

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Lung cancer is the most frequent malignancy, and non-small cell lung cancer (NSCLC) is its most common pathological type. Molecular targeted therapy has been testified to be effective in intervening in the occurrence and development of malignancies. This study investigates the effect of lncRNA Regulatory Factor X3- antisense RNA 1 (RFX3-AS1) in NSCLC progression. The RFX3-AS1 profile in NSCLC tissues and cells was measured by quantitative reverse transcription PCR (qRT-PCR). The RFX3-AS1 overexpression model was constructed. The cell counting kit-8 (CCK-8) experiment and cell colony formation assay were adopted to test cell viability. The cell apoptosis was determined by flow cytometry (FCM). Cell migration and invasion were monitored by the Transwell assay, and Western blot was implemented to verify the protein profiles of signal transducer and activator of transcription 3 (STAT3), E-cadherin, Vimentin and N-cadherin. In vivo , we validated the impact of RFX3-AS1 overexpression on the NSCLC xenograft mouse model. The targeting relationships between RFX3-AS1 and miR-577, miR-577 and STAT3 were confirmed by the dual-luciferase reporter assay. The results manifested that overexpressing RFX3-AS1 markedly facilitated NSCLC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and suppressed cell apoptosis. In contrast, miR-577, which was a downstream target of RFX3-AS1, dramatically impeded the malignant biological behaviors of NSCLC cells. STAT3 was a direct target of miR-577, and it was negatively regulated by the latter. STAT3 activation reversed miR-577-mediated anti-tumor roles. In brief, RFX3-AS1 aggravated NSCLC progression by regulating the miR-577/STAT3 axis.

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MicroRNA‑4500 suppresses tumor progression in non‑small cell lung cancer by regulating STAT3

Cited by 8 publications

References 40 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

MiR-199a-5p–HIF-1α-STAT3 Positive Feedback Loop Contributes to the Progression of Non-Small Cell Lung Cancer

Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis

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