Abstract

Objectives Recently, immunotherapy and microRNA have shown much more promises in oncology research, inspiring new hope for a cure for various malignancies. Specifically, the function and mechanisms of action of pembrolizumab have been investigated in many cancers, but not in laryngeal squamous cell carcinoma. The present study thus focused on the effect of hsa-miR-128a on pembrolizumab in laryngeal cancer cells as well as tried to elucidate the mechanisms that may mediate this effect. Methods Hep2 and AMC-HN8 cell lines were utilized to create stable cell lines that overexpressing hsa-miR-128a. Using the immunotherapy assay, the contribution of hsa-miR-128a to pembrolizumab sensitivity was evaluated. By performing the dual luciferase assay and quantitative real-time polymerase chain reaction, the possible mechanisms of hsa-miR-128a were identified. Results Hsa-miR-128a was overexpressed in laryngeal cancer cell lines successfully. The immunotherapy assay revealed that upregulating hsa-miR-128a augmented the effect of pembrolizumab. Moreover, hsa-miR-128a targeted BMI-1 and might played a role in the p53 pathway. Conclusion Hsa-miR-128a boosted the effect of pembrolizumab on laryngeal cancer cells, perhaps via the p53 pathway. Therefore, hsa-miR-128a might be a novel target in laryngeal cancer treatment.

Highlights

  • Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer in the United States, with an estimated 65,410 new cases and 14,620 deaths in 2019 [1]

  • Laryngeal squamous cell carcinoma is among the most malignant cancers and accounts for 1%–2.5% of all malignancies [2], while limited-stage HNSCCs are often curable with surgical resection or definitive radiotherapy and chemotherapy, such as platinum-based regimens, recurrent, and metastatic HNSCCs are associated with poor prognosis, with a 1-year survival rate of approximately 50% [3]

  • The most commonly used cell lines of laryngeal squamous cell carcinoma, Hep-2 cell line, and AMC-HN8 cell line were cultured appropriately according to the instructions

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Summary

Introduction

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer in the United States, with an estimated 65,410 new cases and 14,620 deaths in 2019 [1]. Laryngeal squamous cell carcinoma is among the most malignant cancers and accounts for 1%–2.5% of all malignancies [2], while limited-stage HNSCCs are often curable with surgical resection or definitive radiotherapy and chemotherapy, such as platinum-based regimens, recurrent, and metastatic HNSCCs are associated with poor prognosis, with a 1-year survival rate of approximately 50% [3]. The 5-year overall survival rate of laryngeal cancer is less than 60% [4]. In cases of advanced stage or recurrent tumors, neither traditional chemotherapy nor targeted therapy can improve prognosis; so, researchers must seek novel approaches

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