Wang Yujia, Qin Zhen, Chen Yiwen, Zheng Yunfei, Jia Lingfei
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Cancers (Basel). 2023 Dec 11;15(24):5792. doi: 10.3390/cancers15245792.
The altered expression of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. We performed a high-throughput analysis of lncRNA expression in strictly selected pairs of metastatic head and neck squamous cell carcinoma (HNSCC) and non-metastatic HNSCC samples. We identified a novel lncRNA, which was highly expressed in metastatic HNSCC, named Metastasis Associated Squamous Cell Carcinoma 1 (MASCC1), for further study. Using qRT-PCR, we further compared MASCC1 expression in 60 HNSCC samples. The results show that high expression of MASCC1 in patients with HNSCC was related to poor prognosis. In vitro, MASCC1 knockdown (KD) inhibited HNSCC proliferation, migration, invasion, and tumor sphere formation, while promoting apoptosis. In vivo, MASCC1 KD inhibited HNSCC growth and lymph node metastasis. Mechanistically, MASCC1 acted as a competing endogenous RNA (ceRNA) by binding to miR-195, subsequently regulating the expression of Cyclin D1, BCL-2, and YAP1. Moreover, miR-195 overexpression rescued the effects of MASCC1 on the biological behaviors of HNSCC. Taken together, our results suggest that is a novel oncogene that can predict the prognosis of patients with HNSCC and is a potential therapeutic target for HNSCC intervention.
长链非编码RNA（lncRNA）表达的改变与人类肿瘤发生相关。我们对严格挑选的转移性头颈部鳞状细胞癌（HNSCC）和非转移性HNSCC样本对中的lncRNA表达进行了高通量分析。我们鉴定出一种在转移性HNSCC中高表达的新型lncRNA，命名为转移相关鳞状细胞癌1（MASCC1），用于进一步研究。使用qRT-PCR，我们进一步比较了60例HNSCC样本中MASCC1的表达。结果表明，HNSCC患者中MASCC1的高表达与预后不良相关。在体外，MASCC1敲低（KD）抑制HNSCC的增殖、迁移、侵袭和肿瘤球形成，同时促进细胞凋亡。在体内，MASCC1 KD抑制HNSCC生长和淋巴结转移。机制上，MASCC1通过与miR-195结合作为竞争性内源RNA（ceRNA），随后调节细胞周期蛋白D1、BCL-2和YAP1的表达。此外，miR-195过表达挽救了MASCC1对HNSCC生物学行为的影响。综上所述，我们的结果表明，MASCC1是一种新型癌基因，可预测HNSCC患者的预后，是HNSCC干预的潜在治疗靶点。
