Aberrant expression of long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) has been detected in human colorectal cancer (CRC). This study aimed to investigate the role of CDKN2B-AS1 and the underlying mechanism in human CRC. Gain- and loss-of-function assays were performed to explore the role of CDKN2B-AS1 in the malignant behavior of HCT116 and SW480 CRC cells in vitro and in vivo. RNA pull-down assay was conducted to identify the target of CDKN2B-AS1 in CRC cells. The physical and functional interactions between CDKN2B-AS1 and the target were examined. CDKN2B-AS1 inhibited CRC cell proliferation and migration while promoting apoptosis in vitro via activation of mitogen-activated protein kinase kinases (MEK)/extracellular signal-regulated kinase (ERK)/p38 signaling. CDKN2B-AS1 bound to mitogen-activated protein kinase (MAPK) inactivator dual-specificity phosphatase 1 (DUSP1) in CRC cells. In contrast to CDKN2B-AS1, DUSP1 promoted CRC cell proliferation, suppressed apoptosis and inactivated MEK/ERK/p38 signaling in CRC cells. Furthermore, CDKN2B-AS1 overexpression attenuated DUSP1 expression in normal colonic myofibroblasts and CRC cells. Overexpression of DUSP1 effectively countered the activation of MEK/ERK/p38 signaling induced by CDKN2B-AS1 overexpression or further blocked MEK/ERK/p38 signaling suppressed by CDKN2B-AS1 silencing. In the mouse xenograft model, CDKN2B-AS1 suppressed CRC growth, whereas DUSP1 promoted CRC growth. CDKN2B-AS1 induced cell apoptosis while suppressing EMT (epithelial-mesenchymal transition), whereas DUSP1 suppressed cell apoptosis while inducing EMT in CRC, as evidenced by the alterations in the protein levels of apoptosis and EMT markers in tumor tissue samples. CDKN2B-AS1 regulates CRC cell growth and survival by targeting MAPK inactivator DUSP1.

中文翻译：

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CDKN2B 反义 RNA 1 通过靶向 MAPK 灭活剂双特异性磷酸酶 1 抑制人结直肠癌的肿瘤生长。

已在人类结直肠癌 (CRC) 中检测到长链非编码 RNA 细胞周期蛋白依赖性激酶抑制剂 2B 反义 RNA 1 (CDKN2B-AS1) 的异常表达。本研究旨在探讨 CDKN2B-AS1 在人类 CRC 中的作用及其潜在机制。进行了功能获得和功能丧失检测，以探索 CDKN2B-AS1 在体外和体内 HCT116 和 SW480 CRC 细胞恶性行为中的作用。进行RNA pull-down测定以鉴定CRC细胞中CDKN2B-AS1的靶标。检查了 CDKN2B-AS1 和目标之间的物理和功能相互作用。CDKN2B-AS1 抑制 CRC 细胞增殖和迁移，同时通过激活丝裂原活化蛋白激酶激酶 (MEK)/细胞外信号调节激酶 (ERK)/p38 信号传导在体外促进细胞凋亡。CDKN2B-AS1 与 CRC 细胞中的丝裂原活化蛋白激酶 (MAPK) 灭活剂双特异性磷酸酶 1 (DUSP1) 结合。与 CDKN2B-AS1 相比，DUSP1 促进 CRC 细胞增殖，抑制细胞凋亡并灭活 CRC 细胞中的 MEK/ERK/p38 信号。此外，CDKN2B-AS1 过表达减弱了正常结肠肌成纤维细胞和 CRC 细胞中 DUSP1 的表达。DUSP1 的过表达有效地对抗了 CDKN2B-AS1 过表达诱导的 MEK/ERK/p38 信号的激活，或进一步阻断了 CDKN2B-AS1 沉默抑制的 MEK/ERK/p38 信号。在小鼠异种移植模型中，CDKN2B-AS1 抑制 CRC 生长，而 DUSP1 促进 CRC 生长。CDKN2B-AS1 在抑制 EMT（上皮间质转化）的同时诱导细胞凋亡，而 DUSP1 在诱导 CRC 中的 EMT 的同时抑制细胞凋亡，肿瘤组织样本中细胞凋亡和 EMT 标志物的蛋白质水平的改变证明了这一点。CDKN2B-AS1 通过靶向 MAPK 灭活剂 DUSP1 调节 CRC 细胞的生长和存活。