Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation

Chan, Lai Sheung; Lung, Hong Lok; Ngan, Roger K.C.; Lee, Anne W.M.; Tsao, Sai Wah; Lo, Kwok Wai; Kahn, Michaël; Lung, Maria Li; Wieser, Rotraud; Mak, Nai Ki

doi:10.3390/ijms21155495

Cited by 9 publications

(8 citation statements)

References 52 publications

(84 reference statements)

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“…Previous in vitro experiments have confirmed that EBV-infected epithelial cells activate the Hedgehog signaling pathway to cause stem cell phenotype (Port et al, 2013). The Wnt signaling pathway also plays an essential role in the maintenance of cancer stem cells (Chan et al, 2020). Also, it is possible to target Th1 and Th2 cell differentiation, Th17 cell differentiation, and the T cell receptor signaling pathway (not in the top 10) with CTLA4, CD28, NF-kB, and GM-CSF to affect the changes of the immune microenvironment.…”

Section: Discussionmentioning

confidence: 93%

Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma

Wang

et al. 2021

Front. Mol. Biosci.

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Introduction: tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs, are divided into two categories: tRNA-related fragments (tRFs) and tRNA halves (tiRNAs). Abnormal expression of tsRNAs has been found in diverse cancers, which indicates that further understanding of the function of tsRNAs will help identify new biomarkers and potential therapeutic targets. Until now, the underlying roles of tsRNAs in primary nasopharyngeal carcinoma (NPC) are still unknown.Methods: tRF and tiRNA sequencing was performed on four pairs of NPC tissues and healthy controls. Thirty pairs of NPC samples were used for quantitative real-time polymerase chain reaction (qRT-PCR) verification, and the ROC analysis was used to evaluate the diagnostic efficiency initially. Target prediction and bioinformatics analysis of validated tRFs and tiRNAs were conducted to explore the mechanisms of tsRNAs in NPC’s pathogenesis.Results: A total of 158 differentially expressed tRFs and tiRNAs were identified, of which 88 are upregulated and 70 are downregulated in NPC. Three validated tRFs in the results of qRT-PCR were consistent with the sequencing data: two upregulations (tRF-1:28-Val-CAC-2 and tRF-1:24-Ser-CGA-1-M3) and one downregulation (tRF-55:76-Arg-ACG-1-M2). The GO and KEGG pathway enrichment analysis showed that the potential target genes of validated tRFs are widely enriched in cancer pathways. The related modules may play an essential role in the pathogenesis of NPC.Conclusions: The tsRNAs may become a novel class of biological diagnostic indicators and possible targets for NPC.

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Section: Discussionmentioning

confidence: 93%

Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma

Wang

et al. 2021

Front. Mol. Biosci.

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“…Expression of miR-449a-5p was shown to be downregulated in tumor tissue compared with normal tissue in nasopharyngeal carcinoma [17]. Studies show that miR-449a has a suppressive effect on the progression, migration, and sphere formation of nasopharyngeal cancer cells [33,34]. In nasopharyngeal cancer, this miRNA was found to suppress LDH oncogenic activity [33].…”

Section: Discussionmentioning

confidence: 99%

miRNAs as Biomarkers for Diagnosing and Predicting Survival of Head and Neck Squamous Cell Carcinoma Patients

Piotrowski

Zhu

Saccon

et al. 2021

Cancers

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Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. These tumors originate from epithelial cells of the upper aerodigestive tract. HNSCC tumors in different regions can have significantly different molecular characteristics. While many microRNAs (miRNAs) have been found to be involved in the regulation of the carcinogenesis and pathogenesis of HNSCC, new HNSCC related miRNAs are still being discovered. The aim of this study was to explore potential miRNA biomarkers that can be used to diagnose HNSCC and prognose survival of HNSCC patients. For this purpose, we chose a panel of 12 miRNAs: miR-146a-5p, miR-449a, miR-126-5p, miR-34a-5p, miR-34b-5p, miR-34c-5p, miR-217-5p, miR-378c, miR-6510-3p, miR-96-5p, miR-149-5p, and miR-133a-5p. Expression of these miRNAs was measured in tumor tissue and neighboring healthy tissue collected from patients diagnosed with HNSCC (n = 79) in either the oral cavity, oropharynx, or larynx. We observed a pattern of differentially expressed miRNAs at each of these cancer locations. Our study showed that some of these miRNAs, separately or in combination, could serve as biomarkers distinguishing between healthy and tumor tissue, and their expression correlated with patients’ overall survival.

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“…Cell migration assay was performed as described previously [29]. Briefly, NPC cells with/without treatment were seeded onto 6.5 mm transwell inserts with 8.0 µm pores polycarbonate membrane (Corning, #3442, Corning, NY, USA).…”

Section: Transwell Migration Assaymentioning

confidence: 99%

“…The transfection of precursor miRNA (pre-miRNA) was performed as previously described [29]. Briefly, the cells were transfected with 50 nM pre-miR-134 (Ambion; P/N: AM17100; ID: AM20391) for 48 h with Lipofectamin 2000.…”

Section: Cell Transfectionmentioning

confidence: 99%

“…In contrast, much fewer studies have addressed the modulation of miRNAs by Wnt/βcatenin signaling [26]. In our previous studies, ICG-001-mediated blockage of canonical Wnt/β-catenin signaling could inhibit the growth of CSC-enriched NPC tumor spheres via the miR-145/SOX2 axis [27] and inhibit the migration of NPC cells via the miR-150/CD44 axis [28] and the miR-96/EVI1/miR-449a axis [29]. Here we further investigated the anti-cancer effects of ICG-001 in NPC with a focus on its role in tumor metastasis.…”

Section: Introductionmentioning

confidence: 99%

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The CBP/β-Catenin Antagonist, ICG-001, Inhibits Tumor Metastasis via Blocking of the miR-134/ITGB1 Axis-Mediated Cell Adhesion in Nasopharyngeal Carcinoma

Chen

Chiang

Chan

et al. 2022

Cancers

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Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated malignancy ranking as the 23rd most common cancer globally, while its incidence rate ranked the 9th in southeast Asia. Tumor metastasis is the dominant cause for treatment failure in NPC and metastatic NPC is yet incurable. The Wnt/β-catenin signaling pathway plays an important role in many processes such as cell proliferation, differentiation, epithelial–mesenchymal transition (EMT), and self-renewal of stem cells and cancer stem cells (CSCs). Both the EMT process and CSCs are believed to play a critical role in cancer metastasis. We here investigated whether the specific CBP/β-catenin Wnt antagonist, IGC-001, affects the metastasis of NPC cells. We found that ICG-001 treatment could reduce the adhesion capability of NPC cells to extracellular matrix and to capillary endothelial cells and reduce the tumor cell migration and invasion, events which are closely associated with distant metastasis. Through a screening of EMT and CSC-related microRNAs, it was found that miR-134 was consistently upregulated by ICG-001 treatment in NPC cells. Very few reports have mentioned the functional role of miR-134 in NPC, except that the expression was found to be downregulated in NPC. Transient transfection of miR-134 into NPC cells reduced their cell adhesion, migration, and invasion capability, but did not affect the growth of CSC-enriched tumor spheres. Subsequently, we found that the ICG-001-induced miR-134 expression resulting in downregulation of integrin β1 (ITGB1). Such downregulation reduced cell adhesion and migration capability, as demonstrated by siRNA-mediated knockdown of ITGB1. Direct targeting of ITGB1 by miR-134 was confirmed by the 3′-UTR luciferase assay. Lastly, using an in vivo lung metastasis assay, we showed that ICG-001 transient overexpression of miR-134 or stable overexpression of miR-134 could significantly reduce the lung metastasis of NPC cells. Taken together, we present here evidence that modulation of Wnt/β-catenin signaling pathway could inhibit the metastasis of NPC through the miR-134/ITGB1 axis.

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Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation

Cited by 9 publications

References 52 publications

Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma

Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma

miRNAs as Biomarkers for Diagnosing and Predicting Survival of Head and Neck Squamous Cell Carcinoma Patients

The CBP/β-Catenin Antagonist, ICG-001, Inhibits Tumor Metastasis via Blocking of the miR-134/ITGB1 Axis-Mediated Cell Adhesion in Nasopharyngeal Carcinoma

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