Zheng Jian, Zhao Zhuochen, Ren Huijun, Wang Yongfeng, Meng Xianchun, Zhang Wenjing, Zhang Cai, Ming Liang, Lu Xiubo
Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2022 Apr 7;12:872033. doi: 10.3389/fonc.2022.872033. eCollection 2022.
Long noncoding RNAs (LncRNAs) play complex but important roles in the progression of various tumors. This study aimed to elucidate the functional mechanisms of the HLA complex group 11 (HCG11) in nasopharyngeal carcinoma (NPC).
HCG11 levels in NPC specimens were determined by fluorescence hybridization (FISH) and qPCR. Proliferation, apoptosis, and metastasis of NPC cells were determined using CCK8, colony formation, annexin V-PI, and transwell assays. A murine tumor xenograft model was used to investigate the regulatory function of HCG11 in NPC , and immunohistochemical staining was used to determine the Ki-67 level in tumors. The target relationships between HCG11, microRNA miR-490-3p, and MAPK kinase kinase 9 (MAP3K9) were detected using bioinformatics, qPCR, western blotting, and luciferase reporter assays.
HCG11 was highly expressed in NPC tissues and was positively associated with tumor stage, lymphatic metastasis, and poor prognosis. Functionally, HCG11 knockdown inhibited proliferation and migration and induced apoptosis of NPC cells. Mechanistically, miR-490-3p is a direct target of HCG11, oncogenic functions of HCG11 in NPC cell proliferation and migration can be partially reversed by the miR-490-3p inhibitor. HCG11 significantly increased mitogen-activated protein kinase MAPK kinase 9 (MAP3K9) levels by inhibiting miR-490-3p.
HCG11 facilitates NPC progression MAP3K9 signaling by sponging miRNA-490-3p, which may contribute to new prognostic markers and promising therapeutic targets.
长链非编码RNA(LncRNAs)在各种肿瘤进展中发挥着复杂而重要的作用。本研究旨在阐明人类白细胞抗原复合体组11(HCG11)在鼻咽癌(NPC)中的功能机制。
采用荧光杂交(FISH)和qPCR检测NPC标本中HCG11水平。使用CCK8、集落形成、膜联蛋白V-碘化丙啶和Transwell实验检测NPC细胞的增殖、凋亡和转移情况。采用小鼠肿瘤异种移植模型研究HCG11在NPC中的调控功能,并用免疫组化染色法检测肿瘤组织中的Ki-67水平。利用生物信息学、qPCR、蛋白质免疫印迹和荧光素酶报告基因实验检测HCG11、微小RNA miR-490-3p和丝裂原活化蛋白激酶激酶激酶9(MAP3K9)之间的靶向关系。
HCG11在NPC组织中高表达,且与肿瘤分期、淋巴转移及预后不良呈正相关。在功能上,敲低HCG11可抑制NPC细胞的增殖和迁移,并诱导其凋亡。机制上,miR-490-3p是HCG11的直接靶点,miR-490-3p抑制剂可部分逆转HCG11在NPC细胞增殖和迁移中的致癌功能。HCG11通过抑制miR-490-3p显著提高丝裂原活化蛋白激酶MAPK激酶9(MAP3K9)的水平。
HCG11通过结合miRNA-490-3p促进NPC进展及MAP3K9信号传导,这可能有助于发现新的预后标志物和有前景的治疗靶点。