The MiR-17-92 Gene Cluster is a Blood-Based Marker for Cancer Detection in Non-Small-Cell Lung Cancer

Yang, Chenghao; Jia, Xiaoyu; Zhou, Jinbao; Sun, Qiangling

doi:10.1016/j.amjms.2020.05.004

Cited by 18 publications

(15 citation statements)

References 41 publications

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“…Lung cancer is one disease with relatively high morbidity and mortality, of which NSCLC accounts for a large proportion. 1 Therefore, the study on the corresponding molecular mechanism responsible for proliferation and metastasis in NSCLC is very important for the early diagnosis and treatment. The abnormal expression of lncRNAs is closely associated with the tumorgenesis and progression of NSCLC, and lncRNAs may be potentially efficient biomarkers for early diagnosis and therapy of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…As the common type of lung cancer, non-small cell lung cancer (NSCLC) is one of the most severe diseases threatening human health. 1 NSCLC possesses the characteristics of high malignancy and aggressiveness, and the metastases of lymph nodes and different organs are prone to occur in advanced stages of NSCLC 2,3 Accompanied by the advancement of molecular biology in lung cancer, related driver genes and targeted therapy have become the focus of lung cancer research. 4 Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is one of the most pivotal signaling pathways for cell survival, differentiation and apoptosis in the body.…”

Section: Introductionmentioning

confidence: 99%

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LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

Wu¹,

Yang²,

Li³

et al. 2021

OTT

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Background Non-small cell lung cancer (NSCLC) is one of the most common malignancies with the highest morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) are recently recognized as noteworthy regulators of different tumors, counting NSCLC. However, the biological functions and regulatory mechanism of lncRNA WT1-AS in NSCLC progression still stay uninvestigated. Methods WT1-AS and miR-494-3p levels in NSCLC cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). In the current study, the regulatory effects of WT1-AS/miR-494-3p axis on cellular behaviors of NSCLC cell lines (A549 and NCI-H1975) were evaluated by a variety of methods. Cell counting kit-8 (CCK-8) and EDU assays were adopted to assess NSCLC cell proliferation. Tunnel staining and flow cytometry assay were applied to determine cell apoptosis and cell cycle distribution. Besides, cell migration and invasion abilities were analyzed by performing wound healing and transwell assays. Meanwhile, the levels of key proteins related to NSCLC cell apoptosis and PTEN/PI3K/AKT pathway were examined using Western blot assay. In addition, luciferase reporter assays were used to determine the interaction between WT1-AS and miR-494-3p or miR-494-3p and PTEN. Results Visibly downregulated WT1-AS in NSCLC cell lines was obtained from Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and further verified by performing RT-qPCR. Besides, miR-494-3p was the downstream target gene of WT1-AS and obviously upregulated miR-494-3p in NSCLC cell lines was confirmed. WT1-AS overexpression suppressed cell proliferation, migration and invasion abilities while enhanced cell apoptosis of A549 and NCI-H1975 cells. Furthermore, upregulation of miR-494-3p distinctly reversed these inhibitory effects of WT1-AS overexpression on the tumorigenesis and progression of NSCLC. In addition, WT1-AS promoted PTEN expression and thereby inhibited activation of PI3K/AKT pathway by sponging miR-494-3p. Conclusion To conclude, lncRNA WT1-AS impeded cell proliferation, migration, invasion but accelerated cell apoptosis via negatively regulating miR-494-3p to mediate PTEN/PI3K/AKT pathway in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

Wu¹,

Yang²,

Li³

et al. 2021

OTT

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“…Multiple miRNAs, including the miR-17-92 family have been implicated in various types of malignancies ( 33 , 34 ). Abnormal expression of miR-17-92 family members is closely associated with the occurrence and progression of lung cancer ( 35 , 36 ). The present study investigated whether one miR-17-92 family member, miR-17-5p, may be involved in modulating NSCLC drug sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin B enhances apoptosis in gefitinib resistant non‑small cell lung cancer by modulating the miR‑17‑5p/STAT3 axis

Zheng

Tang

et al. 2021

Mol Med Rep

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Tyrosine kinase inhibitors, such as gefitinib, are currently widely used as targeted therapeutics for non-small cell lung cancer (NSCLC). Although drug resistance has become a major obstacle to successful treatment, mechanisms underlying resistance to gefitinib remain unclear. Therefore, the present study aimed to investigate the impact of adjunctive cucurbitacin B (CuB) on gefitinib resistance (GR) in the PC9 cell line, including identifying underlying mechanisms. Reverse transcription-quantitative PCR demonstrated significant downregulation of microRNA (miR)-17-5p expression in GR PC9 cells (PC9/GR), and this could be reversed by CuB. During combination treatment with CuB and gefitinib at IC 25 , PC9/GR cell proliferation was downregulated, and apoptosis was upregulated. The presence of a miR-17-5p inhibitor negated the effects of CuB and gefitinib, whereas the presence of a miR-17-5p mimic enhanced them. Luciferase assays demonstrated that the hypothetical target gene, signal transducer and activator of transcription 3 ( STAT3 ), was directly targeted by miR-17-5p. Moreover, significant elevation of the STAT3 protein and phosphorylation levels in PC9/GR cells was reversed by the addition of CuB, despite a lack of change in STAT3 transcription level. During combined treatment with CuB and gefitinib at IC 25 , the STAT3 protein expression was negatively associated with the expression of miR-17-5p. Overexpression of STAT3 increased proliferation and decreased apoptosis and the protein levels of apoptosis-related factors cleaved caspase-3 and cleaved caspase-9 of PC9/GR cells. Findings indicated that STAT3 protein and phosphorylation levels became elevated in response to gefitinib, and that CuB-induced miR-17-5p expression led to STAT3 degradation, thereby ameliorating GR. In summary, CuB reduced the proliferation of GR PC9 cells by modulating the miR-17-5p/STAT3 axis, and may represent a promising potential novel strategy for the reversal of GR.

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“…MiR-17-92 cluster might be useful as a potential serum biomarker for the early detection of gastric cancer [ 5 ], and it also involved in the occurrence and development of bladder cancer [ 6 ]. Besides, miR-17-92 cluster could likely serve as a diagnostic marker in NSCLC [ 7 ]. These researches suggested that miR-17-92 cluster serving as a biomarker in some cancers could provide patients with precision therapy.…”

Section: Introductionmentioning

confidence: 99%

Downregulated miR-18a and miR-92a synergistically suppress non-small cell lung cancer via targeting Sprouty 4

et al. 2022

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As a novel noncoding RNA cluster, miR-17-92 cluster include six members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a. Dysregulation of miR-17-92 has been proved to be connected with the advancement of a series of human diseases, but the roles of miR-17-92 cluster in non-small cell lung cancer (NSCLC) have not been absolutely elaborated. Herein, we determined that miR-17-92 cluster were upregulated significantly in NSCLC tissues, and the cell proliferation, migration and cycle progression of NSCLC were also facilitated under the function of miR-17-92 cluster. Sprouty 4 ( SPRY4 ) was a direct target of miR-92a, and its overexpression restrained the exacerbation of NSCLC induced by miR-92a. Furthermore, the tumor xenograft assay showed that miR-92a facilitated tumor growth by inhibiting the expression of SPRY4 and mediating Epithelial-Mesenchymal Transition (EMT) in vivo . Finally, we looked into the synergistic effects of miR-92a and miR-18a on NSCLC, and found that antagomiR-18a treatment arrested the tumor growth rate of xenografted mice markedly.

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The MiR-17-92 Gene Cluster is a Blood-Based Marker for Cancer Detection in Non-Small-Cell Lung Cancer

Cited by 18 publications

References 41 publications

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

Cucurbitacin B enhances apoptosis in gefitinib resistant non‑small cell lung cancer by modulating the miR‑17‑5p/STAT3 axis

Downregulated miR-18a and miR-92a synergistically suppress non-small cell lung cancer via targeting Sprouty 4

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