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Abstract：
UNASSIGNED: Circular RNAs (circRNAs) have been identified as potential biomarkers and therapeutic targets for various types of cancer, including Oral squamous cell carcinoma (OSCC). Hsa_circRNA_101036 was found to function as a cancer suppressor gene in OSCC; however, the underlying regulatory mechanism remains unclear. We investigated the role of hsa_circRNA_101036 in OSCC development and progression and explored its potential as a therapeutic target.
UNASSIGNED: We performed a bioinformatics analysis and used experimental approaches to investigate the regulatory mechanism of hsa_circRNA_101036. The database StarBase v.2.0 was used to predict potential target-miRNAs of hsa_circRNA_101036. The levels of hsa_circRNA_101036, miR-21-3p, and TMTC2 expression in samples of OSCC cancer tissue (n = 15) and adjacent tissue (n = 15) were determined. We also examined the effects of hsa_circRNA_101036 overexpression on OSCC cell lines by using cell viability, migration, and invasion assays. The proportions of apoptotic cells and the reactive oxygen species (ROS) levels were analyzed by flow cytometry. We also investigated how hsa_circRNA_101036 overexpression affected the levels of miR-21-3p and TMTC2, and endoplasmic reticulum (ER) stress in OSCC cells.
UNASSIGNED: The levels of hsa_circRNA_101036 and TMTC2 expression were significantly lower, while miR-21-3p expression was higher in tumor tissues and OSCC cells when compared to adjacent tissues and normal oral fibroblasts, respectively. The levels of HIF-1α and miR-21-3p expression were significantly increased under conditions of hypoxia, while the levels of hsa_circRNA_101036 and TMTC2 were decreased. The expression levels of proteins associated with ER stress, the proportions of apoptotic cells, and the levels of ROS were all increased by hypoxia stimulation. In addition, overexpression of hsa_circRNA_101036, but not mutant hsa_circRNA_101036, was found to enhance the effect of hypoxia on HSC3 and OECM-1 cells. Hsa_circRNA_101036 overexpression suppressed tumor growth and induced ER stress. Finally, knockdown of miR-21-3p had the same effect as overexpression of hsa_circRNA_101036.
UNASSIGNED: Our findings suggest that hsa_circRNA_101036 plays a critical role in the development and progression of OSCC. Overexpression of hsa_circRNA_101036 aggravated ER stress, and increased cell apoptosis and ROS production in OSCC under hypoxic conditions. Hsa_circRNA_101036 up-regulated TMTC2 expression by sponging miR-21-3p in OSCC.
UNASSIGNED: We performed a bioinformatics analysis and used experimental approaches to investigate the regulatory mechanism of hsa_circRNA_101036. The database StarBase v.2.0 was used to predict potential target-miRNAs of hsa_circRNA_101036. The levels of hsa_circRNA_101036, miR-21-3p, and TMTC2 expression in samples of OSCC cancer tissue (n = 15) and adjacent tissue (n = 15) were determined. We also examined the effects of hsa_circRNA_101036 overexpression on OSCC cell lines by using cell viability, migration, and invasion assays. The proportions of apoptotic cells and the reactive oxygen species (ROS) levels were analyzed by flow cytometry. We also investigated how hsa_circRNA_101036 overexpression affected the levels of miR-21-3p and TMTC2, and endoplasmic reticulum (ER) stress in OSCC cells.
UNASSIGNED: The levels of hsa_circRNA_101036 and TMTC2 expression were significantly lower, while miR-21-3p expression was higher in tumor tissues and OSCC cells when compared to adjacent tissues and normal oral fibroblasts, respectively. The levels of HIF-1α and miR-21-3p expression were significantly increased under conditions of hypoxia, while the levels of hsa_circRNA_101036 and TMTC2 were decreased. The expression levels of proteins associated with ER stress, the proportions of apoptotic cells, and the levels of ROS were all increased by hypoxia stimulation. In addition, overexpression of hsa_circRNA_101036, but not mutant hsa_circRNA_101036, was found to enhance the effect of hypoxia on HSC3 and OECM-1 cells. Hsa_circRNA_101036 overexpression suppressed tumor growth and induced ER stress. Finally, knockdown of miR-21-3p had the same effect as overexpression of hsa_circRNA_101036.
UNASSIGNED: Our findings suggest that hsa_circRNA_101036 plays a critical role in the development and progression of OSCC. Overexpression of hsa_circRNA_101036 aggravated ER stress, and increased cell apoptosis and ROS production in OSCC under hypoxic conditions. Hsa_circRNA_101036 up-regulated TMTC2 expression by sponging miR-21-3p in OSCC.
摘要：
■环状RNA（circularRNAs，circRNAs）已被确定为各种类型癌症的潜在生物标志物和治疗靶标，包括口腔鳞状细胞癌（OSCC）。Hsa_circRNA_101036被发现在OSCC中作为癌症抑制基因发挥作用；然而，潜在的监管机制仍不清楚。我们研究了hsa_circRNA_101036在OSCC发展和进展中的作用，并探索了其作为治疗靶标的潜力。
■我们进行了生物信息学分析，并使用实验方法研究了hsa_circRNA_101036的调节机制。数据库StarBasev.2.0用于预测hsa_circRNA_101036的潜在靶miRNA。hsa_circRNA_101036,miR-21-3p,测定OSCC癌组织(n=15)和邻近组织(n=15)样品中的TMTC2表达。我们还通过使用细胞活力检查了hsa_circRNA_101036过表达对OSCC细胞系的影响，迁移,和入侵检测。通过流式细胞术分析凋亡细胞的比例和活性氧（ROS）水平。我们还研究了hsa_circRNA_101036过表达如何影响OSCC细胞中miR-21-3p和TMTC2的水平以及内质网（ER）应激。
■hsa_circRNA_101036和TMTC2表达水平显著降低,而与癌旁组织和正常口腔成纤维细胞相比，miR-21-3p在肿瘤组织和OSCC细胞中的表达更高，分别。缺氧条件下HIF-1α和miR-21-3p表达水平显著升高,而hsa_circRNA_101036和TMTC2的水平降低。与内质网应激相关的蛋白质的表达水平，凋亡细胞的比例，缺氧刺激后ROS水平均升高。此外,发现hsa_circRNA_101036的过表达，而不是突变体hsa_circRNA_101036的过表达，可以增强缺氧对HSC3和OECM-1细胞的影响。hsa_circRNA_101036过表达抑制肿瘤生长并诱导ER应激。最后,miR-21-3p的敲低与hsa_circRNA_101036的过表达具有相同的效果。
■我们的发现表明，hsa_circRNA_101036在OSCC的发生和发展中起着至关重要的作用。hsa_circRNA_101036过表达加重内质网应激,在低氧条件下，OSCC中的细胞凋亡和ROS产生增加。Hsa_circRNA_101036通过增强OSCC中的miR-21-3p上调TMTC2表达。
■我们进行了生物信息学分析，并使用实验方法研究了hsa_circRNA_101036的调节机制。数据库StarBasev.2.0用于预测hsa_circRNA_101036的潜在靶miRNA。hsa_circRNA_101036,miR-21-3p,测定OSCC癌组织(n=15)和邻近组织(n=15)样品中的TMTC2表达。我们还通过使用细胞活力检查了hsa_circRNA_101036过表达对OSCC细胞系的影响，迁移,和入侵检测。通过流式细胞术分析凋亡细胞的比例和活性氧（ROS）水平。我们还研究了hsa_circRNA_101036过表达如何影响OSCC细胞中miR-21-3p和TMTC2的水平以及内质网（ER）应激。
■hsa_circRNA_101036和TMTC2表达水平显著降低,而与癌旁组织和正常口腔成纤维细胞相比，miR-21-3p在肿瘤组织和OSCC细胞中的表达更高，分别。缺氧条件下HIF-1α和miR-21-3p表达水平显著升高,而hsa_circRNA_101036和TMTC2的水平降低。与内质网应激相关的蛋白质的表达水平，凋亡细胞的比例，缺氧刺激后ROS水平均升高。此外,发现hsa_circRNA_101036的过表达，而不是突变体hsa_circRNA_101036的过表达，可以增强缺氧对HSC3和OECM-1细胞的影响。hsa_circRNA_101036过表达抑制肿瘤生长并诱导ER应激。最后,miR-21-3p的敲低与hsa_circRNA_101036的过表达具有相同的效果。
■我们的发现表明，hsa_circRNA_101036在OSCC的发生和发展中起着至关重要的作用。hsa_circRNA_101036过表达加重内质网应激,在低氧条件下，OSCC中的细胞凋亡和ROS产生增加。Hsa_circRNA_101036通过增强OSCC中的miR-21-3p上调TMTC2表达。
