Nucleotide‐binding domain, leucine‐rich repeat family with a caspase activation and recruitment domain 3 (NLRC3) participates in both immunity and cancer. The aim of this study was to determine the role of NLRC3 in human hepatocellular carcinoma (HCC) and the underlying mechanisms. We collected human liver tissues from nonalcoholic steatohepatitis (NASH), HCC, and adjacent normal tissues to characterize the pattern of NLRC3 expression by real‐time quantitative polymerase chain reaction and immunohistochemistry. Then, we used the HCC cell line, HuH‐7, transfected with small interfering RNA to silence the NLRC3 expression. 5‐Ethynyl‐2'‐deoxyuridine assay, scratch assay, and transwell invasion assay were used for assessing proliferation, migration, and invasion, respectively. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were conducted to assess cell apoptosis. The expression of NLRC3 was reduced in human HCC tissues, compared with normal liver and nonalcoholic steatohepatitis tissues. After knocking down of NLRC3, the proliferation, migration, and invasion were increased in HuH‐7 cells. And flow cytometry and TUNEL assay showed that HuH‐7 cell apoptosis was suppressed after NLRC3 knockdown. As for the underlying mechanisms, knockdown of NLRC3 in HuH‐7 cells was associated with the activation of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway under interleukin‐6 (IL‐6) stimulation. NLRC3 expression was downregulated in human HCC tissues. NLRC3 silencing in HuH‐7 cells can promote the proliferation, migration, and invasion of hepatocellular carcinoma cells. JAK2/STAT3 pathway activation induced by IL‐6 may be the underlying mechanism for HCC when NLRC3 expression is silenced. And the invasion of HuH‐7 cells was partially suppressed by the STAT3 specific inhibitor (cryptotanshinone). Therefore, NLRC3 may play a significant role in HCC and might be a therapeutic target for the treatment of HCC.

中文翻译：

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NLRC3 沉默通过 IL-6/JAK2/STAT3 通路激活加速肝细胞癌细胞的侵袭。

核苷酸结合域，具有半胱天冬酶激活和募集域 3 (NLRC3) 的富含亮氨酸的重复家族参与免疫和癌症。本研究的目的是确定 NLRC3 在人肝细胞癌 (HCC) 中的作用及其潜在机制。我们从非酒精性脂肪性肝炎 (NASH)、HCC 和邻近正常组织中收集人肝组织，通过实时定量聚合酶链反应和免疫组织化学来表征 NLRC3 表达模式。然后，我们使用转染了小干扰 RNA 的 HCC 细胞系 HuH-7 来沉默 NLRC3 表达。5-乙炔基-2'-脱氧尿苷测定、划痕测定和transwell侵袭测定分别用于评估增殖、迁移和侵袭。进行流式细胞术和末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL) 测定以评估细胞凋亡。与正常肝脏和非酒精性脂肪性肝炎组织相比，人 HCC 组织中 NLRC3 的表达降低。敲低NLRC3后，HuH-7细胞的增殖、迁移和侵袭增加。流式细胞术和 TUNEL 检测表明，敲除 NLRC3 后 HuH-7 细胞凋亡受到抑制。至于潜在机制，HuH-7细胞中NLRC3的敲低与白细胞介素6（IL-6）刺激下Janus激酶2/信号转导和转录激活因子3（JAK2/STAT3）通路的激活有关。NLRC3 表达在人 HCC 组织中下调。HuH-7 细胞中的 NLRC3 沉默可以促进增殖、迁移、和肝细胞癌细胞的侵袭。当 NLRC3 表达沉默时，IL-6 诱导的 JAK2/STAT3 通路激活可能是 HCC 的潜在机制。HuH-7 细胞的侵袭被 STAT3 特异性抑制剂（隐丹参酮）部分抑制。因此，NLRC3 可能在 HCC 中发挥重要作用，并可能成为治疗 HCC 的治疗靶点。