Department of Oral & Maxillofacial Surgery, Shenzhen Stomatology Hospital Affiliated to Shenzhen University, Shenzhen City 518000, GuangDong Province, China.
Department of Stomatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen City 518033, GuangDong Province, China.
J Immunol Res. 2022 Jun 2;2022:4589182. doi: 10.1155/2022/4589182. eCollection 2022.
The role of miRNAs as crucial components in carcinogenesis has been well documented. However, whether and how miR-214 influences oral cancer cells' drug resistance remains to be elucidated, and its downstream targets are still under investigation. Hence, this research is aimed at determining miR-214 and ULK1 expression in oral cancer before and after chemotherapy and their correlations with cancer cell growth. Human oral normal epithelial cells and human tongue squamous cell carcinoma CAL-27 cells were cultured to detect miR-214 and ULK1 levels. It was found that before chemotherapy, miR-214 was higher, while ULK1 was underexpressed in CAL-27 cells, versus normal epithelial cells. After chemotherapy, miR-214 decreased obviously in CAL-27 cells, while ULK1 level increased significantly. In addition, autophagy-related genes (Beclin 1, mTOR, and P53) in CAL-27 cells were found to be significantly inhibited before chemotherapy and were obviously increased after chemotherapy. Moreover, to further determine the impacts of miR-214 and ULK1 on oral cancer cell growth after chemotherapy, the two were overexpressed or silenced in CAL-27 cells after transfection. We found that ULK1 could effectively decrease the activity and invasion of CAL-27 cells and increase their apoptosis level, while miR-214 could antagonize its antitumor effect. Therefore, miR-214 can be used as an early prognostic biomarker for oral cancer, and ULK1 is a new candidate therapeutic target.
miRNAs 作为致癌作用的关键组成部分的作用已得到充分证实。然而，miR-214 是否以及如何影响口腔癌细胞的耐药性仍有待阐明，其下游靶标仍在研究中。因此，本研究旨在确定化疗前后口腔癌中 miR-214 和 ULK1 的表达及其与癌细胞生长的相关性。培养人口腔正常上皮细胞和人舌鳞癌细胞 CAL-27 以检测 miR-214 和 ULK1 水平。结果发现，化疗前 CAL-27 细胞中 miR-214 水平较高，而 ULK1 表达较低，而正常上皮细胞中则相反。化疗后，CAL-27 细胞中 miR-214 明显降低，而 ULK1 水平明显升高。此外，CAL-27 细胞中自噬相关基因（Beclin 1、mTOR 和 P53）在化疗前明显受到抑制，化疗后明显增加。此外，为了进一步确定 miR-214 和 ULK1 对化疗后口腔癌细胞生长的影响，在转染后在 CAL-27 细胞中过表达或沉默这两种基因。结果发现，ULK1 可有效降低 CAL-27 细胞的活性和侵袭能力，增加其凋亡水平，而 miR-214 可拮抗其抗肿瘤作用。因此，miR-214 可作为口腔癌的早期预后生物标志物，而 ULK1 是新的候选治疗靶点。
