Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
Int J Mol Med. 2018 May;41(5):2660-2668. doi: 10.3892/ijmm.2018.3451. Epub 2018 Feb 1.
B‑cell CLL/lymphoma 6 member B (BCL6B), a BCL6‑homologous gene, has been reported to be a tumor suppressor that is silenced in a variety of human cancers, including colorectal cancer (CRC). Although it was recently demonstrated that reduced expression of BCL6B is associated with tumor stage and lymph node metastasis in CRC, little is known on whether BCL6B contributes to CRC development, or the related underlying mechanism. The aim of the present study was to detect BCL6B expression in CRC cells, and determine the molecular mechanisms underlying the role of BCL6B in CRC development by investigating cell proliferation and migration in vitro. As a result, BCL6B expression was found to be notably repressed in CRC cells compared with normal intestinal epithelial cells by reverse transcription‑polymerase chain reaction and western blot analysis. CRC cell proliferation was significantly inhibited by BCL6B upregulation, as indicated by MTT and colony‑forming assays. Cell apoptosis was markedly induced, as indicated by flow cytometry, and BCL6B‑transfected CRC cells exhibited decreased migration ability. Additionally, BCL6B overexpression diminished the phosphorylation level of AKT in CRC cells. These effects of BCL6B were empowered by treatment with the specific phosphoinositide 3 kinase (PI3K)/AKT inhibitor LY294002. Furthermore, overexpression of BCL6B resulted in upregulation of E‑cadherin and downregulation of cyclin D1 and matrix metalloproteinase‑9, which were strongly enhanced by LY294002. In conclusion, the findings of the present study demonstrated that BCL6B suppressed the proliferation and migration of CRC cells indirectly, via inhibition of PI3K.
B 细胞慢性淋巴细胞白血病/淋巴瘤 6 成员 B（BCL6B）是 BCL6 的同源基因，已被报道为一种肿瘤抑制因子，在多种人类癌症中失活，包括结直肠癌（CRC）。尽管最近已经证明 BCL6B 的表达降低与 CRC 中的肿瘤分期和淋巴结转移有关，但对于 BCL6B 是否有助于 CRC 的发展或相关的潜在机制知之甚少。本研究旨在检测 CRC 细胞中的 BCL6B 表达，并通过体外研究细胞增殖和迁移来确定 BCL6B 在 CRC 发展中的作用的分子机制。结果显示，与正常肠上皮细胞相比，CRC 细胞中的 BCL6B 表达明显受到抑制，通过逆转录聚合酶链反应和 Western blot 分析证实。MTT 和集落形成测定表明，BCL6B 的上调显著抑制了 CRC 细胞的增殖。通过流式细胞术明显诱导了细胞凋亡，并且 BCL6B 转染的 CRC 细胞表现出降低的迁移能力。此外，BCL6B 的过表达降低了 CRC 细胞中 AKT 的磷酸化水平。通过使用特定的磷脂酰肌醇 3 激酶（PI3K）/AKT 抑制剂 LY294002 处理，增强了 BCL6B 的这些作用。此外，BCL6B 的过表达导致 E-钙粘蛋白的上调和 cyclin D1 和基质金属蛋白酶-9 的下调，LY294002 强烈增强了这些作用。总之，本研究的结果表明，BCL6B 通过抑制 PI3K 间接抑制 CRC 细胞的增殖和迁移。
