NLRC5 promotes tumorigenesis by regulating the PI3K/AKT signaling pathway in cervical cancer

• Published in: Scientific reports 2024-07, Vol.14 (1), p.15353-12, Article 15353
• Main Authors: Ling, Lin, Chen, Jiahua, Zhan, Lei, Fu, Juanjuan, He, Runhua, Wang, Wenyan, Wei, Bing, Ma, Xiaofeng, Cao, Yunxia
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/67; 631/67/1517; 631/67/1517/1371; Adult; AKT protein; Autophagy; Carcinogenesis - genetics; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cervical cancer; Correlation analysis; Female; Gene Expression Regulation, Neoplastic; Human papillomavirus; Humanities and Social Sciences; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Lymph nodes; Metastases; Middle Aged; multidisciplinary; NLRC5; Phenotypes; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; Science; Science (multidisciplinary); Signal Transduction; Tumorigenesis; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-66153-3

Cervical cancer (CC) is the fourth most common cancer among women worldwide. NLR Family CARD Domain Containing 5 (NLRC5) plays an important role in tumorigenesis. However, its effect and mechanism in CC remains unclear. In this study, we aimed to investigate the function of NLRC5 in CC. NLRC5 was found to be down-regulated in CC tissues compared with normal cervical tissues. However, patients with higher NLRC5 expression had better prognosis, patients with higher age, HPV infection, lymph node metastasis, recurrence and histological grade had worse prognosis. Univariate and multivariate analyses showed NLRC5 to be a potential prognostic indicator for CC. Pearson correlation analysis showed that NLRC5 might exert its function in CC through autophagy related proteins, especially LC3. In vitro experiments demonstrated that NLRC5 inhibited LC3 levels and promoted the proliferation, migration, and invasion of CC cells by activating the PI3K/AKT signaling pathway. Treatment with LY294002 reversed the above phenotype. Taken together, our finding suggested that NLRC5 would participate in cervical tumorigenesis and progression by regulating PI3K/AKT signaling pathway. In addition, NLRC5 and LC3 combined as possible predictors in CC.