Tumor suppressor microRNAs in lung cancer: An insight to signaling pathways and drug resistance

Asghariazar, Vahid; Sakhinia, Ebrahim; Mansoori, Behzad; Mohammadi, Ali; Baradaran, Behzad

doi:10.1002/jcb.29295

Cited by 16 publications

(18 citation statements)

References 112 publications

(217 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…The development of lung cancer is a multistep process involved in the accumulation of genetic and epigenetic changes that lead to DNA damage and eventually the conversion of epithelial cells into cancer cells ( Asghariazar et al, 2019 ). Lung cancer has become one of the most common cancers because of lifestyle changes and increased risk factors ( Hosseini et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Zhu

Yuan

2021

Front. Cell Dev. Biol.

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Erlotinib (ER), as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has a significant therapeutic effect in lung cancers. However, EGFR TKI resistance inevitably occurs after treatment for approximately 12 months, which weakens its antitumor effect. Here, we identified miR-185-3p as a significantly downregulated microRNA responsible for acquired EGFR TKI resistance in cells and patients with lung cancer. qRT-PCR and Western Blot were performed to determine the relative expression of miR-185-3p in ER-resistant tumor tissues and cells. The viability and apoptosis of lung cancer cells were evaluated by Cell Counting Kit-8 (CCK8) assay and flow cytometry, respectively. The binding between miR-185-3p and liver-type phosphofructokinase (PFKL) was verified by dual luciferase assay. It was found that overexpression of miR-185-3p conferred ER sensitivity in lung cancer cell lines. MiR-185-3p was downregulated in ER-resistant lung cancer cells (H1299/ER and A549/ER). MiR-185-3p inhibited proliferation and induced cell apoptosis in ER-resistant cells. Mechanistically, miR-185-3p downregulation contributed to ER resistance through upregulating the PFKL. Moreover, Mesenchymal to epithelial transition (MET) oncoprotein promoted EGFR-TKI resistance by regulating miR-185-3p and PFKL. These findings revealed a novel mechanism in which downregulation of miR-185-3p may induce overexpression of PFKL and MET and confer ER resistance in lung cells. Combination of PFKL/MET inhibitors and EGFR TKIs could be a rational therapeutic approach for lung cancer patients with EGFR mutation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Zhu

Yuan

2021

Front. Cell Dev. Biol.

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“…CCNA2 promotes invasion and migration of non-small cell lung cancer cells through integrin αvβ3 signaling pathway [40]. miR-26a/b inhibits directly migration, invasion, and proliferation of lung cancer cells by targeting CDC6 [41]. CKS1B is a lung cancer-related gene, knockdown of which results in a significant decrease in lung cancer cell proliferation, invasion and migration [42].…”

Section: The Critical State Of Luscmentioning

confidence: 99%

“…Nucleus other miR-26a/b inhibits directly migration, invasion, and proliferation of lung cancer cells by targeting CDC6 [41].…”

Section: Cdc6 13mentioning

confidence: 99%

Identifying critical state of complex diseases by single-sample Kullback–Leibler divergence

2020

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Background: Developing effective strategies for signaling the pre-disease state of complex diseases, a state with high susceptibility before the disease onset or deterioration, is urgently needed because such state usually followed by a catastrophic transition into a worse stage of disease. However, it is a challenging task to identify such predisease state or tipping point in clinics, where only one single sample is available and thus results in the failure of most statistic approaches. Methods: In this study, we presented a single-sample-based computational method to detect the early-warning signal of critical transition during the progression of complex diseases. Specifically, given a set of reference samples which were regarded as background, a novel index called single-sample Kullback-Leibler divergence (sKLD), was proposed to explore and quantify the disturbance on the background caused by a case sample. The pre-disease state is then signaled by the significant change of sKLD. Results: The novel algorithm was developed and applied to both numerical simulation and real datasets, including lung squamous cell carcinoma, lung adenocarcinoma, stomach adenocarcinoma, thyroid carcinoma, colon adenocarcinoma, and acute lung injury. The successful identification of pre-disease states and the corresponding dynamical network biomarkers for all six datasets validated the effectiveness and accuracy of our method. Conclusions: The proposed method effectively explores and quantifies the disturbance on the background caused by a case sample, and thus characterizes the criticality of a biological system. Our method not only identifies the critical state or tipping point at a single sample level, but also provides the sKLD-signaling markers for further practical application. It is therefore of great potential in personalized pre-disease diagnosis.

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“…Lung cancer development is a multistage process that includes the accumulation of genetic and epigenetic changes, which cause damage to DNA and finally turns lung epithelial cells into cancerous cells (Asghariazar, Sakhinia, Mansoori, Mohammadi, & Baradaran, 2019). Lung cancer is the most fatal cancer among Americans (Larsen & Minna, 2011).…”

Section: Introductionmentioning

confidence: 99%

Restoration of miR‐330 expression suppresses lung cancer cell viability, proliferation, and migration

Mohammadi

Mansoori

Duijf

et al. 2020

Journal Cellular Physiology

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Lung cancer is one of the most common cancers and its incidence is rising around the world. Various studies suggest that miR-330 acts as a tumor-suppressor microRNA (miRNA) in different types of cancers, but precisely how has remained unclear. In this study, we investigate miR-330 expression in lung cancer patient samples, as well as in vitro, by studying how normalization of miR-330 expression affects lung cancer cellular phenotypes such as viability, apoptosis, proliferation, and migration. We establish that low miR-330 expression predicts poor lung cancer prognosis. Stable restoration of reduced miR-330 expression in lung cancer cells reduces cell viability, increases the fraction of apoptotic cells, causes G2/M cell cycle arrest, and inhibits cell migration. These findings are substantiated by increased mRNA and protein expression of markers for apoptosis via the intrinsic pathway, such as caspase 9, and decreased mRNA and protein expression of markers for cell migration, such as vimentin, C-X-C chemokine receptor type 4, and matrix metalloproteinase 9. We showed that reduced miR-330 expression predicts poor lung cancer survival and that stable restoration of miR-330 expression in lung cancer cells has a broad range of tumor-suppressive effects. This indicates that miR-330 is a promising candidate for miRNA replacement therapy for lung cancer patients.

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Tumor suppressor microRNAs in lung cancer: An insight to signaling pathways and drug resistance

Cited by 16 publications

References 112 publications

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Identifying critical state of complex diseases by single-sample Kullback–Leibler divergence

Restoration of miR‐330 expression suppresses lung cancer cell viability, proliferation, and migration

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