Nasopharyngeal carcinoma (NPC) is a highly prevalent malignant tumor of the head and neck originated from epithelial cells lining the nasopharynx, imposing an enormous threat to human health throughout the world [1], [2]. NPC exhibits a specific ethnic difference and geographical distribution, with a predominance of cases occurring in Southeast Asia, particularly Southern China and Northern Africa [3], [4]. Available evidence has proved that genetic susceptibility, environmental factors including Epstein-Barr virus (EBV) infection, and dysregulation of tumor-promoting or tumor-suppressing genes are important contributors to the occurrence and development of NPC [5]. Most of NPC patients are at an advanced stage at the time of the initial diagnosis and often presents with local recurrence and high frequency of distant metastasis, leading to a high rate of treatment failure and eventually death [6], [7], [8]. Recently, more and more scientific attention has been focused on the role of inflammation in cancer progression [9]. Increasing studies have well-documented the close association of chronic inflammation with the pathogenesis and progression of various tumors including NPC [10], [11]. Accordingly, there is an urgent need for researchers to identify effective therapeutic targets for NPC with the aim of alleviating proliferation and inflammatory response in NPC cells.

Chitinase 3 like-1 (CHI3L1), also called YKL‐40, located on human chromosome 1q32.1, encodes a 40-kDa secreted glycoprotein with a polypeptide chain consisting of 383 amino acids [12]. CHI3L1, belonging to the family of 18-glycosyl hydrolase, lacks chitinolytic activity due to a mutation in the chitinase-3-like catalytic domain [13], and is secreted by many cell types, like endothelial, inflammatory, and cancer cells [14], [15]. Available evidence has proved that CHI3L1 plays a vital role in inflammation, cell proliferation, apoptosis, metastasis, and angiogenesis in cancer cells [14], [16], [17], [18]. Also, high expression of CHI3L1 is positively correlated with worse prognosis and functions as an oncogenic gene in many types of cancer, such as prostate cancer, breast cancer, and colorectal cancer [19], [20], [21]. However, little literature is available to illustrate the biological role of CHI3L1 in NPC cells.

In the present study, we examined two NPC datasets (GSE64634 and GSE12452) from the Gene Expression Omnibus (GEO) and identified common differentially expressed genes (DEGs) in the two datasets above. Among the common DEGs, CHI3L1 was selected. According to Gene ontology (GO) enrichment and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses, CHI3L1 is related to inflammatory response, cell proliferation, positive regulation of protein kinase B (Akt) signaling, and is enriched in the PI3K-Akt pathway. It has been reported that NF-κB, one of the downstream effectors of Akt pathway, is a key link between inflammation and cancer [22], [23], [24]. Thus, we propose a hypothesis that CHI3L1 induces NF-κB-dependent inflammatory response and promotes cell proliferation by activating the Akt pathway in nasopharyngeal carcinoma cells. Then, we performed a series of functional experiments to validate this hypothesis.