Abstract
ARAF is a member of the RAF kinase family that is necessary for mitogen-activated protein kinase (MAPK) activation in various malignancies, including lung, colorectal, pancreatic, and breast cancers. As the most common biliary tract tumor, gallbladder cancer (GBC) seriously harms human health while the function of ARAF in GBC remains elusive. Here, we found that ARAF expression was upregulated in gallbladder cancer tissues. In vitro, ARAF silencing mediated by RNA interference effectively inhibited cell proliferation, colony formation, migration, and invasion of GBC cells. Moreover, knocking down ARAF suppressed tumor growth in vivo. Our results indicated that ARAF functions as an oncogene in GBC and, thus, could be a potential therapeutic target for GBC.
Highlights
Gallbladder cancer (GBC) is an aggressive malignancy of the biliary tract that originates from the gallbladder and cystic duct mucosal epithelia [1]
ARAF Expression Is Upregulated in GBC Tissues
To compare ARAF mRNA expression between GBC and nontumoral samples, RT-qPCR was performed, and the average ARAF mRNA expression of 12 nontumoral tissues was defined as the baseline expression of normal tissues
Summary
Gallbladder cancer (GBC) is an aggressive malignancy of the biliary tract that originates from the gallbladder and cystic duct mucosal epithelia [1]. As the most common biliary tract cancer, GBC accounts for 80%-95% of all biliary malignancies and has a dismal prognosis [2, 3]. The recent optimization of medical auxiliary examinations and the widespread application of laparoscopic cholecystectomy have significantly increased the detection rate of gallbladder cancer; its prognosis has not improved because of latestage diagnoses, high recurrence rates, and metastatic features [4]. Surgical resection remains the most effective treatment for GBC, most patients are diagnosed with advanced-stage disease, meaning they are not candidates for surgery [5, 6]. Clearing the underlying molecular mechanisms of GBC tumorigenesis and metastasis will provide a theoretical basis for improving its diagnosis and treatment
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