digital-analysis-immunostaining-zw10-interacting-protein-human-lung

Digital Analysis of Immunostaining of ZW10 Interacting Protein in Human Lung Tissues

The purpose of this study is to introduce a methodology of the immunostaining of human lung tissues, followed by whole-slide digital scanning and image ...

wuhan university

Lung cancer is the leading cause of mortalities among all types of cancer. Therefore, the screening of biomarkers that are related with the progression of lung cancer is crucial for early diagnosis and efficient therapy of lung cancer. In the present study, bioinformatic analysis identified replication factor C 5 (RFC5) as a potential novel oncogene in lung cancer. RFC5 functions as a clamp loader and is involved in DNA replication and repair. Analysis of public databases and reverse transcription-quantitative polymerase chain reaction indicated that RFC5 was significantly increased in tumor tissues compared with adjacent normal tissues. A high RFC5 expression was observed to be associated with more aggressive malignant clinicopathological features, including higher T stage, more advanced regional lymph node metastasis and a higher probability of relapse. Notably, there were notable differences in overall survival (OS), first progression and post-progression survival between the high RFC5 expression group and low RFC5 expression group. Univariate and multivariate Cox regression analyses indicated that RFC5 was an independent risk factor that was associated with poorer OS and disease-free survival. According to GSEA, several gene sets that are associated with cell cycle and DNA damage were enriched in the RFC5 overexpression group, which indicated that RFC5 might promote the proliferation of lung cancer cells. Our finding indicated that RFC5 might be a novel prognostic biomarker of lung cancer, and it might be serve as a potential diagnosis and therapy target for lung cancer in the future.

Identification of RFC5 as a novel potential prognostic biomarker in lung cancer through bioinformatics analysis.

Metastatic disease remains the primary cause of death for individuals with T cell acute lymphoblastic leukemia (T-ALL). microRNAs (miRNAs) play important roles in the pathogenesis of T-ALL by inhibiting gene expression at posttranscriptional levels. The goal of the current project is to identify any significant miRNAs in T-ALL metastasis. We observed miR-146b-5p to be downregulated in T-ALL patients and cell lines, and bioinformatics analysis implicated miR-146b-5p in the hematopoietic system. miR-146b-5p inhibited the migration and invasion in T-ALL cells. Interleukin-17A (IL-17A) was predicted to be a target of miR-146b-5p; this was confirmed by luciferase assays. Interestingly, T-ALL patients and cell lines secreted IL-17A and expressed the IL-17A receptor (IL-17RA). IL-17A/IL-17RA interactions promoted strong T-ALL cell migration and invasion responses. Gene set enrichment analysis (GSEA) and quantitative polymerase chain reaction (qPCR) analysis indicated that matrix metallopeptidase-9 (MMP9), was a potential downstream effector of IL-17A activation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was also implicated in this process. Moreover, IL-17A activation promoted T-ALL cell metastasis to the liver in IL17A  mouse models. These results indicate that reduced miR-146b-5p expression in T-ALL may lead to the upregulation of IL-17A, which then promotes T-ALL cell migration and invasion by upregulating MMP9 via NF-κB signaling.

Loss of miR-146b-5p promotes T cell acute lymphoblastic leukemia migration and invasion via the IL-17A pathway.

Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are involved in a variety of physiological and pathological processes. We analyzed 11 data sets from Gene Expression Omnibus Database and found that MMP7 and MMP15 were highly expressed in multiple carcinomas. GSE13204 showed that MMP7 and MMP15 were overexpressed in acute myeloid leukemia (AML) patients. The Cancer Genome Atlas data set exhibited that high expression of MMP7 or MMP15 in bone marrow (BM) of AML patients predicted poor overall survival. The χ  test results indicated that high expression level of MMP7 and MMP15 were correlated with high-risk stratification and high BM blast cell percentage in AML patients. To confirm these findings, we performed reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and found that MMP7 and MMP15 were highly expressed in three AML cell lines. Further study showed that MMP7 and MMP15 were highly expressed both in BM and peripheral blood in collected AML samples compared with healthy individuals. Additionally, long noncoding RNA (lncRNA) microarray of BM samples of AML patients revealed that multiple lncRNAs were correlated with MMP7 and MMP15, suggesting that lncRNAs might be involved in the pathogenesis of AML via modulating MMPs. In conclusion, our study uncovers the potential roles of MMP7 and MMP15 in the prognosis of AML.

Article	Year
Identification of RFC5 as a novel potential prognostic biomarker in lung cancer through bioinformatics analysis. Oncology letters\| PubMed ID: 30214556	2018
Loss of miR-146b-5p promotes T cell acute lymphoblastic leukemia migration and invasion via the IL-17A pathway. Journal of cellular biochemistry\| PubMed ID: 30362152	2019
The prognostic value of matrix metalloproteinase-7 and matrix metalloproteinase-15 in acute myeloid leukemia. Journal of cellular biochemistry\| PubMed ID: 30809850	2019

Yin Qian

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