MiR‑148a modulates HLA‑G expression and influences tumor apoptosis in esophageal squamous cell carcinoma

Chen, Quan; Luo, Guanghua; Zhang, Xiaoying

doi:10.3892/etm.2017.5058

Cited by 11 publications

(14 citation statements)

References 40 publications

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“…Manuscript to be reviewed regulating HLA-G expression (Chen et al 2017). Together with our findings in this study, miR-520a and miR-148a might probably serve as key regulators of ESCC carcinogenesis and nCRT response.…”

Section: Discussionsupporting

confidence: 73%

Peer Review #3 of "Transcriptional factor regulation network and competitive endogenous RNA (ceRNA) network determining response of esophageal squamous cell carcinomas to neoadjuvant chemoradiotherapy (v0.1)"

2019

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Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery benefits survival for patients with esophageal squamous cell carcinomas (ESCC) compared with surgery alone, but the clinical outcomes of nCRT are heterogeneous. This study aimed to elucidate transcriptional factor (TF) regulation network and competitive endogenous RNA (ceRNA) network determining response of ESCC to nCRT. Materials and Methods: RNA microarray data of GSE59974 and GSE45670 were analyzed to investigate the significant changes of lincRNAs, miRNAs, mRNAs in responders and non-responders of nCRT in ESCC. Functional and enrichment analyses were conducted by clusterProfiler. The target lincRNAs and mRNAs of miRNAs were predicted by miRWalk. The ceRNA and TF regulatory networks were constructed using Cytoscape. Results: Differentially expressed genes between responders and non-responders mainly enriched in biological process including Wnt signaling pathway and regulation of cell development and morphogenesis involved in differentiation. Besides, these genes showed enrichment in molecular function of glycosaminoglycan binding, metalloendopeptidase inhibitor and growth factor activity. KEGG analysis enriched these genes in pathways of neurotrophin signaling pathway, cell adhesion molecules and Wnt signaling pathway. We also constructed ceRNA network and TF network regulating response of ESCC to nCRT. Core regulatory miRNAs were miR-520a, miR-548am, miR-3184, miR-548d, miR-4725, miR-148a, miR-4659a and key regulatory TFs included MBNL1, SLC26A3, BMP4, ZIC1 and ANKRD7. Conclusion: We identified significantly altered lincRNAs, miRNAs and mRNAs involved in the nCRT response of ESCC. In addition, the ceRNA regulatory network of lincRNA-miRNA-mRNA and TF regulatory network were constructed, which would elucidate novel molecular mechanisms determining nCRT response of ESCC, thus providing promising clues for clinical therapy.

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Section: Discussionsupporting

confidence: 73%

Peer Review #3 of "Transcriptional factor regulation network and competitive endogenous RNA (ceRNA) network determining response of esophageal squamous cell carcinomas to neoadjuvant chemoradiotherapy (v0.1)"

2019

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“…Interestingly, high PD‐L1 expression was a significant independent prognostic factor in patients with ESCC and high HLA class I expression 42 . In a preclinical study, MiR‐148a was shown to modulate HLA‐G expression and influence tumor cell apoptosis in an ESCC model 43 …”

Section: Human Leucocyte Antigen In Esccmentioning

confidence: 99%

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

et al. 2020

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Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD‐1) or programmed death‐ligand 1 (PD‐L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD‐L1 expression on tumors, tumor‐infiltrating lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.

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“…Previous studies have identified the involvement of various miRNAs in the initiation and progression of oral cancer, including miR-31, miR-139, miR-195, miR-21, miR-221 and miR-455 (34–42). Numerous studies have reported the downregulation of miR-148a in various cancers, including gastric and breast cancers, and esophageal squamous cell carcinoma (22,24), suggesting it exhibits tumor suppressor roles in cancer cells. In the present study, miR-148a was observed to be downregulated in the OSCC cell line, SCC-9 compared with normal cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that HLA-G is a target of miR-148a (22–24). HLA-G serves an important role in the development and metastasis to lymph nodes of OSCC (25).…”

Section: Introductionmentioning

confidence: 99%

miR‑148a modulates the viability, migration and invasion of oral squamous cell carcinoma cells by regulating HLA‑G expression

2019

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Oral squamous cell carcinoma (OSCC) is a common malignancy of the oral and maxillofacial regions. MicroRNAs (miRs) are a group of endogenous small noncoding RNAs that inhibit gene expression by binding to the mRNA of target genes, and serve important roles in numerous biological processes. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect gene and protein expression levels, respectively. Cell proliferation, migration and invasion were detected using MTT, wound healing and Matrigel assays, respectively. The association between miR-148a and human leukocyte antigen-G (HLA-G) was analyzed using Targetscan and Luciferase reporter assays. In the present study, miR-148a was revealed to be significantly downregulated in OSCC cells. To further investigate the functions of miR-148a in OSCC, the viability, migration, and invasive abilities of SCC-9 cells were investigated following transfection with miR-148a mimics or miR-148a inhibitor. It was revealed that transfection with miR-148a mimics significantly reduced the viability, migration and invasion of cells, whereas miR-148a inhibitor significantly enhanced these properties. In addition, HLA-G was identified as a direct target of miR-148a and demonstrated to be downregulated in OSCC cells. Furthermore, it was revealed that transfection with miR-148a mimics decreased the expression levels of HLA-G mRNA and protein in SCC-9 cells, whereas transfection with miR-148a inhibitor increased the expression of HLA-G mRNA and protein. The results indicated that there was an association between miR-148a and HLA-G expression, and suggested that miR-148a may be a potential target in the treatment of OSCC.

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MiR‑148a modulates HLA‑G expression and influences tumor apoptosis in esophageal squamous cell carcinoma

Abstract: Abstract. Esophageal cancer (EC) is a common malignant tumor type, and esophageal squamous cell carcinoma (ESCC)

Cited by 11 publications

References 40 publications

Peer Review #3 of "Transcriptional factor regulation network and competitive endogenous RNA (ceRNA) network determining response of esophageal squamous cell carcinomas to neoadjuvant chemoradiotherapy (v0.1)"

Peer Review #3 of "Transcriptional factor regulation network and competitive endogenous RNA (ceRNA) network determining response of esophageal squamous cell carcinomas to neoadjuvant chemoradiotherapy (v0.1)"

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

miR‑148a modulates the viability, migration and invasion of oral squamous cell carcinoma cells by regulating HLA‑G expression

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