Identification of microRNA differentially expressed in three subtypes of non-small cell lung cancer and in silico functional analysis

Hu, Yan-Jun; Wang, Luqing; Gu, Jingxian; Qu, Kai

doi:10.18632/oncotarget.20218

Cited by 21 publications

(18 citation statements)

References 50 publications

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“…44,48,51,54,[56][57][58][59] In NSCLC, miRNA-375 is associated with poor prognosis. 43,44,60 Interestingly, miRNA-375 is strongly associated with the Wnt/ b-catenine pathway 49 and the Hippo pathway, 59,[61][62][63] known to be involved in ICIs resistance. [64][65][66][67][68][69][70] Moreover, miRNA-375 targets the JAK2 gene, 62,71 involved in the IFN-g and TNF-a pathways, key-regulators of cytotoxic CD8C immune response.…”

Section: Discussionmentioning

confidence: 99%

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

et al. 2018

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Immune checkpoint inhibitors, as nivolumab, are used in advanced non-small cell lung cancer (NSCLC). However, no associated biomarker is validated in clinical practice with this drug. We investigated herein immune-related blood markers in patients with advanced NSCLC treated with nivolumab. Plasma of 43 consecutive patients were prospectively collected at time of the diagnosis of cancer, at the initiation of nivolumab and at the first tumour evaluation (2 months). Concentrations of PD-L1 (sPD-L1), soluble PD-L2 (sPD-L2), Interleukine-2 (sIl-2), Interferon-gamma (sIFN-γ), and Granzyme B (sGranB) were quantified by ELISA. Cell free RNA was quantified by Reverse Transcriptase -PCR), and plasmatic microRNAs (miRNAs) were evaluated by targeted sequencing. Expression of PD-L1 on tumour biopsies was performed by immunohistochemistry using E13LN. High sPD-L1 at 2 months and increase of sPD-L1 concentrations were associated with poor response and absence of clinical benefit (nivolumab treatment less than 6 months). The variation of sPD-L1 concentrations were confirmed by RNA quantification. sPD-L1 concentrations were not correlated with PD-L1 expression on corresponding tumour samples. Low sGranB at nivolumab initiation was also associated with poor response. High sPD-L1 and low sGranB were associated with poor progression-free survival (PFS) and overall survival (OS). Low sPD-L2, low sIl-2 and high sIFN-γ were associated with grade 3-4 toxicities. Finally, miRNA screening showed that patients with clinical benefit (n = 9) had down-expression of miRNA-320b and -375 compared to patients with early progression at 2 months (n = 9). In conclusion, our results highlight the interest of circulating biomarkers in patients treated with nivolumab.

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Section: Discussionmentioning

confidence: 99%

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

et al. 2018

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“…miRNAs are small non-coding RNAs that regulate 30% of gene expressions (29,30). miRNAs act as master regulators of gene expression in numerous important biological pathways, including cell cycle, apoptosis and proliferation (31), particularly in cancer.…”

Section: Discussionmentioning

confidence: 99%

miR‑944 inhibits lung adenocarcinoma tumorigenesis by targeting STAT1 interaction

Shi

Hao

et al. 2019

Oncol Lett

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Lung adenocarcinoma (LAC) is a leading cause of cancer-associated mortalities, particularly in developed countries. The aberrant expression of microRNAs (miRNAs) has been proven to regulate numerous diseases in the past two decades. miRNAs have been identified in almost all human cancer types. In the present study, the role of miR-944 in LAC proliferation was examined. It was identified that miR-944 was downregulated in LAC tissues and cells, and miR-944 overexpression inhibited A549 and H1299 cell proliferation, as determined by the Cell Counting Kit-8 and colony formation assay. Signal transducer and activator of transcription 1 (STAT1) was upregulated in LAC tissues and cells. Kaplan-Meier analysis demonstrated that the 5-year overall survival in patients with high STAT1 levels was significantly reduced, compared with patients with negative and low STAT1 expression. STAT1 was the direct target of miR-944. Additionally, a miR-944 mimic inhibited A549 cell growth in vitro . Collectively, these data demonstrate that miR-944 serves a pivotal role in LAC tumor growth by targeting STAT1. The data obtained indicated that miR-944 may be a novel biomarker and could result in potential therapies for LAC.

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“…Since downregulation of miR-203a-3p and let-7-5p family would increase TRIM71 ( Figure 5C), Figure 5B). In the integrated analysis of NSCLC, DNA replication and cell cycle pathways have been detected [128,129], and the WNT and the MAPK signaling pathways were implicated in lung cancer [130]; however, no let-7-5p family hub has been reported on the stage I-II of NSCLC in silico [131][132][133] even though lncRNA interactions were integrated [130,134].…”

Section: Stage I-ii Simulation Of Nsclc and Network Analysismentioning

confidence: 99%

Cancer Simulation from Stage Minus One by Quantum microRNA Language: Lung, Colorectal and Pancreatic Cancers

Fujii¹

2019

Med One

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Background: The second, third, and fourth cases of lethal cause upon cancer are lung cancer, colorectal cancer, and pancreatic cancer, respectively. This trend is not limited to some countries, but is a global problem. To further decrease cancer-related death, early prediction, diagnosis and prognosis of cancer by noninvasive liquid biopsy is an urgent issue for us. It is related with saving lives at a low medical cost and cutting-edged ideas of a neo-medical tool for risk hedge. One of the biomarkers is circulating microRNA (miRNA). miRNA can control gene expression of protein and it is a common factor of tumorigenesis and tumor suppression. Although it has recently been cleared that miRNA panel as a biomarker could be measured and evaluated as an indicator of human diseases, it is remained unclear whether the miRNA biomarker could be evaluated as biological and pathogenic processes, or pharmacologic responses to a therapeutic intervention or not. Methods: To elucidate the implication between miRNA biomarkers and pathogenic processes, time-dependent processes of tumorigenesis in pancreatic, colorectal and lung cancers were investigated through network analysis from minus one stage (or stage zero) of cancer to various cancer stages by algorithm of miRNA entangling target sorting (METS) in silico simulation using quantum miRNA language. Results: We found three different miRNA memory package (MMP) hubs for pathogenic processes among three cancer cases. Conclusions: These computer simulation data suggested that quantum miRNA language would be essential for clinical miRNA biomarker panel to understand its biological, pathological and pharmaceutical characters in cancer.

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Identification of microRNA differentially expressed in three subtypes of non-small cell lung cancer and in silico functional analysis

Cited by 21 publications

References 50 publications

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

miR‑944 inhibits lung adenocarcinoma tumorigenesis by targeting STAT1 interaction

Cancer Simulation from Stage Minus One by Quantum microRNA Language: Lung, Colorectal and Pancreatic Cancers

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