Xiao Mao, Luo Zhi-Yan, Yu Ai-Ru, Xu Ke, Zhou Wei
Department of Respiratory Medicine, Second People's Hospital of Xindu Distrct, Chengdu 610501, Sichuan Province, China.
Department of Emergency, Second People's Hospital of Xindu Distrct, Chengdu 610501, Sichuan Province, China.
World J Gastrointest Oncol. 2025 Jul 15;17(7):108274. doi: 10.4251/wjgo.v17.i7.108274.
Pancreatic cancer (PC) is an aggressive malignancy. As a member of the BTN/BTNL family, BTNL9 has been identified as a tumor suppressor in breast cancer, lung adenocarcinoma, and colon cancer; however, its role and underlying mechanisms in PC remain to be elucidated.
To investigate the role of BTNL9 in the pathogenesis and development of PC.
The difference of BTNL9 expression in cancer and adjacent normal tissues was analyzed by RNA sequencing data from a public database and tissue microarray detection. The relationship between BTNL9 expression and the prognosis of patients was also studied. The effects of BTNL9 on proliferation, metastasis, and cell cycle of PC cells were investigated by phenotypic experiments. The mechanism was investigated by RNA sequencing, western blotting, and immunofluorescence detection.
The mRNA and protein levels of BTNL9 in PC tissues were downregulated compared with normal tissues. Based on survival data from The Cancer Genome Atlas and tissue microarray, BTNL9 was an independent influencing factor for overall survival, and its low expression predicted a shortened overall survival of patients. , BTNL9 could inhibit cell proliferation and metastasis in both PANC-1 and MIA PaCa-2 cells and induce cell cycle arrest in G2/M phases. Downregulation of BTNL9 could activate the cell cycle signaling pathway. Furthermore, overexpression of BTNL9 could significantly inhibit the expression of cell division cycle 20 (CDC20). Rescue experiments demonstrated that overexpression of CDC20 reversed the effect of BTNL9 on the proliferation, metastasis, and cell cycle of PC cells.
The expression of BTNL9 was downregulated in PC, and it has the prediction ability for prognosis. Functionally, BTNL9 exerted an anti-cancer effect by suppressing downstream CDC20 expression in PC.
胰腺癌（PC）是一种侵袭性恶性肿瘤。作为BTN/BTNL家族的成员，BTNL9已被确定为乳腺癌、肺腺癌和结肠癌中的肿瘤抑制因子；然而，其在胰腺癌中的作用及潜在机制仍有待阐明。
探讨BTNL9在胰腺癌发病机制和发展中的作用。
通过公共数据库的RNA测序数据和组织芯片检测分析BTNL9在癌组织和癌旁正常组织中的表达差异。还研究了BTNL9表达与患者预后的关系。通过表型实验研究BTNL9对胰腺癌细胞增殖、转移和细胞周期的影响。通过RNA测序、蛋白质免疫印迹和免疫荧光检测研究其机制。
与正常组织相比，胰腺癌组织中BTNL9的mRNA和蛋白质水平下调。基于癌症基因组图谱的生存数据和组织芯片，BTNL9是总生存的独立影响因素，其低表达预示患者总生存期缩短。BTNL9可抑制PANC-1和MIA PaCa-2细胞的增殖和转移，并诱导细胞周期阻滞在G2/M期。BTNL9的下调可激活细胞周期信号通路。此外，BTNL9的过表达可显著抑制细胞分裂周期蛋白20（CDC20）的表达。挽救实验表明，CDC20的过表达逆转了BTNL9对胰腺癌细胞增殖、转移和细胞周期的影响。
BTNL9在胰腺癌中表达下调，具有预后预测能力。在功能上，BTNL9通过抑制胰腺癌下游CDC20的表达发挥抗癌作用。
