Li Chunxiang, Cai Sanjun, Wang Xishan, Jiang Zheng
Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China.
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Oncotarget. 2015 Oct 6;6(30):29324-34. doi: 10.18632/oncotarget.4979.
The precise role and potential underlying mechanisms of anoctamin 9 (ANO9) remain largely unknown. This study aims to characterize the role and oncogenic mechanisms of ANO9 in stage II and III colorectal cancer (CRC).
We examined the expression of ANO9 in colorectal cancerous tissues and cells using real-time quantitative PCR and immunohistochemistry, respectively. Multiple cellular and molecular approaches such as gene transfection, CCK-8 assay, flow cytometry, and invasion assay were also performed to explore its oncogenic mechanisms. Furthermore, the clinical significance of ANO9 in clinical CRC specimens was assessed by clinical correlation and survival analyses.
Lower expression of ANO9 messenger RNA (mRNA) was frequently detected both in CRC tissues with recurrence and metastasis-derived cell lines. Compared with matched nontumorous tissues, lower expression of ANO9 protein was observed in tumors, which was significantly correlated with tumorigenesis (p < 0.05). In vitro functional studies showed that ANO9 contributed to tumor cell proliferation, apoptosis, and invasion. Moreover, investigation of clinical CRC specimens showed that ANO9 were markedly overexpressed in metastatic tissue compared with primary tissue. Decreased expression of ANO9 was correlated with poor prognostic outcomes.
This study highlighted the role of ANO9 in progression and metastasis of stage II and III CRC. These findings suggested that up-regulation of ANO9, as a metastasis-related gene, could be a novel approach for inhibiting CRC progression.
anoctamin 9（ANO9）的确切作用及潜在机制仍大多未知。本研究旨在明确ANO9在II期和III期结直肠癌（CRC）中的作用及致癌机制。
我们分别使用实时定量PCR和免疫组织化学检测了ANO9在结直肠癌组织和细胞中的表达。还采用了多种细胞和分子方法，如基因转染、CCK-8检测、流式细胞术和侵袭检测，以探究其致癌机制。此外，通过临床相关性和生存分析评估了ANO9在临床CRC标本中的临床意义。
在复发和转移来源的细胞系的CRC组织中，经常检测到ANO9信使核糖核酸（mRNA）表达较低。与配对的非肿瘤组织相比，肿瘤中ANO9蛋白表达较低，这与肿瘤发生显著相关（p < 0.05）。体外功能研究表明，ANO9促进肿瘤细胞增殖、凋亡和侵袭。此外，对临床CRC标本的研究表明，与原发组织相比，ANO9在转移组织中明显过表达。ANO9表达降低与不良预后相关。
本研究强调了ANO9在II期和III期CRC进展和转移中的作用。这些发现表明，上调ANO9作为一种转移相关基因，可能是抑制CRC进展的一种新方法。
