Dataset Information

The anticancer effect of EGFR-targeting artificial microRNA controlled by SLPI promoter in nasopharyngeal carcinoma.

ABSTRACT:

Background

This study intends to use artificial microRNA (recombinant adenovirus vector) targeting epidermal growth factor receptor (EGFR) to inhibit the overexpressed EGFR in nasopharyngeal carcinoma, thereby inhibiting the proliferation and metastasis of nasopharyngeal carcinoma.

Method

The research group verified the expression of EGFR in nasopharyngeal carcinoma through databases, clinical tissues, and cellular pathways. The team first tested the transfection of the recombinant adenovirus by fluorescence microscopy. After adenovirus treatment with different multiplicity of infection (MOI), EGFR level and cell viability in cells were examined by Western blot and MTT assay. Next, the effects of adenovirus (Ad)-SLPI-EGFR on cell proliferation, migration, apoptosis, and related proteins were sequentially examined by EdU, scratch, Transwell, and Western blot. In vivo experiments were performed to evaluate the biological function of EGFR in nasopharyngeal carcinoma.

Result

All three validation pathways showed the increase in EGFR expression in nasopharyngeal carcinoma. Transfection tests showed that the SLPI promoter was specific in CNE2 cells. With the increase in MOI, the inhibition of EGFR expression and cancer cell viability by Ad-SLPI-EGFR was enhanced. Meanwhile, Ad-SLPI-EGFR effectively reduced the proliferation and metastasis of CNE2 cells and affected the expression of related proteins. Furthermore, Ad-SLPI-EGFR inhibited the invasion and metastasis of nasopharyngeal carcinoma in vivo.

Conclusion

Ad-SLPI-EGFR inhibits the expression of EGFR in nasopharyngeal carcinoma cells, and finally achieves the purpose of inhibiting the proliferation and metastasis of cancer cells, which may provide novel targeted intervention for the treatment of nasopharyngeal carcinoma.

SUBMITTER: Dong F

PROVIDER: S-EPMC9701865 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

The anticancer effect of EGFR-targeting artificial microRNA controlled by SLPI promoter in nasopharyngeal carcinoma.

Dong Feilin F Su Lizhong L Tan Jun J Luo Hui H

Journal of clinical laboratory analysis 20221025 11

<h4>Background</h4>This study intends to use artificial microRNA (recombinant adenovirus vector) targeting epidermal growth factor receptor (EGFR) to inhibit the overexpressed EGFR in nasopharyngeal carcinoma, thereby inhibiting the proliferation and metastasis of nasopharyngeal carcinoma.<h4>Method</h4>The research group verified the expression of EGFR in nasopharyngeal carcinoma through databases, clinical tissues, and cellular pathways. The team first tested the transfection of the recombinan ...[more]

PMID: 36284372

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Project description:Non-keratinizing nasopharyngeal carcinoma, the major subtype of nasopharyngeal carcinoma, is characterized by low differentiation and a close relation to Epstein-Barr virus infection, which indicates a link between Epstein-Barr virus oncogenesis and loss of differentiation, and raises our interest in investigating the involvement of Epstein-Barr virus in nasopharyngeal carcinoma dedifferentiation. Our previous study showed abundant expression of an Epstein-Barr virus-encoded microRNA, BART10-3p, in nasopharyngeal carcinoma tissues, but the association between BART10-3p and nasopharyngeal carcinoma differentiation remains unknown. Here, we examined the expression and prognostic value of BART10-3p, and undertook bioinformatics analysis and functional assays to investigate the influence of BART10-3p on nasopharyngeal carcinoma differentiation and proliferation and the underpinning mechanism. Microarray analysis identified BART10-3p as the most significantly upregulated Epstein-Barr virus-encoded microRNA in nasopharyngeal carcinoma tissues and the upregulation was confirmed in two public datasets. The expression of BART10-3p was an independent unfavorable prognosticator in nasopharyngeal carcinoma and its integration with the clinical stage showed improved prognosis predictive performance. Bioinformatics analysis suggested a potential role of BART10-3p in tumor differentiation and progression. Functional assays demonstrated that BART10-3p could promote nasopharyngeal carcinoma cell dedifferentiation, epithelial-mesenchymal transition, and proliferation in vitro, and tumorigenicity in vivo. Mechanistically, BART10-3p directly targeted the 3'UTR of ALK7 and suppressed its expression. Reconstitution of ALK7 rescued BART10-3p-induced malignant phenotypes. Overall, our study demonstrates that BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7, suggesting a promising therapeutic opportunity to reverse the malignant phenotypes of nasopharyngeal carcinoma.

Project description:Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) infection in regions in which it is endemic, including Southern China and Southeast Asia. The high mortality rates of NPC patients with advanced and recurrent disease highlight the urgent need for effective treatments. While recent genomic studies have revealed few druggable targets, the unique interaction between the EBV infection and host cells in NPC strongly implies that targeting EBV may be an efficient approach to cure this virus-associated cancer. Key features of EBV-associated NPC are the persistence of an episomal EBV genome and the requirement for multiple viral latent gene products to enable malignant transformation. Many translational studies have been conducted to exploit these unique features to develop pharmaceutical agents and therapeutic strategies that target EBV latent proteins and induce lytic reactivation in NPC. In particular, inhibitors of the EBV latent protein EBNA1 have been intensively explored, because of this protein's essential roles in maintaining EBV latency and viral genome replication in NPC cells. In addition, recent advances in chemical bioengineering are driving the development of therapeutic agents targeting the critical functional regions of EBNA1. Promising therapeutic effects of the resulting EBNA1-specific inhibitors have been shown in EBV-positive NPC tumors. The efficacy of multiple classes of EBV lytic inducers for NPC cytolytic therapy has also been long investigated. However, the lytic-induction efficiency of these compounds varies among different EBV-positive NPC models in a cell-context-dependent manner. In each tumor, NPC cells can evolve and acquire somatic changes to maintain EBV latency during cancer progression. Unfortunately, the poor understanding of the cellular mechanisms regulating EBV latency-to-lytic switching in NPC cells limits the clinical application of EBV cytolytic treatment. In this review, we discuss the potential approaches for improvement of the above-mentioned EBV-targeting strategies.

Dataset Information

The anticancer effect of EGFR-targeting artificial microRNA controlled by SLPI promoter in nasopharyngeal carcinoma.

Background

Method

Result

Conclusion

Publications

The anticancer effect of EGFR-targeting artificial microRNA controlled by SLPI promoter in nasopharyngeal carcinoma.

Similar Datasets

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