Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Oncol Rep. 2021 May;45(5). doi: 10.3892/or.2021.8012. Epub 2021 Mar 24.
Colorectal cancer (CRC) is one of the most common digestive tract cancers and ~90% of CRC‑related deaths are caused by metastasis. MicroRNA (miR)‑129 has been reported to be involved in the metastasis of various malignant tumors. However, the role of miR‑129 in CRC metastasis remains unclear. The purpose of the present study was to identify the potential functions and mechanisms of action of miR‑129 in CRC progression. The expression of miR‑129 and sex‑determining region Y‑related high‑mobility group‑box 4 (SOX4) was determined in CRC tissues or cell lines by reverse transcription‑quantitative PCR, western blot or immunofluorescence assays. The mechanism underlying the role of miR‑129 in CRC progression was assessed by MTT, wound healing, Transwell, western blot and dual‑luciferase report assays. The results revealed that miR‑129 was significantly decreased, whereas SOX4 was increased, in CRC tissues and cell lines. SW620 and SW480 cells exhibited a higher proliferation, migration and invasion capacity compared with NCM460 cells. miR‑129 overexpression significantly inhibited cell proliferation, migration, invasion and epithelial‑to‑mesenchymal transition (EMT), and it activated the nuclear factor (NF)‑κB signaling pathway in CRC cells, while the inhibition of miR‑129 exerted opposite effects. Additionally, SOX4 was identified as a direct target gene of miR‑129. Taken together, the findings of the present study suggested that miR‑129 may act as a tumor suppressor in CRC by inhibiting CRC cell proliferation, migration, invasion and EMT, in part through targeting the 3'‑untranslated region of SOX4 mRNA, and the mechanism may involve activation of the NF‑κB signaling pathway.
结直肠癌（CRC）是最常见的消化道癌症之一，~90%的 CRC 相关死亡是由转移引起的。miR-129 已被报道参与各种恶性肿瘤的转移。然而，miR-129 在 CRC 转移中的作用尚不清楚。本研究旨在确定 miR-129 在 CRC 进展中的潜在功能和作用机制。通过逆转录定量 PCR、western blot 或免疫荧光分析检测 CRC 组织或细胞系中 miR-129 和性别决定区 Y 相关高迁移率族盒 4（SOX4）的表达。通过 MTT、划痕愈合、Transwell、western blot 和双荧光素酶报告分析评估 miR-129 在 CRC 进展中的作用机制。结果显示，miR-129 在 CRC 组织和细胞系中明显下调，而 SOX4 上调。与 NCM460 细胞相比，SW620 和 SW480 细胞表现出更高的增殖、迁移和侵袭能力。miR-129 过表达显著抑制 CRC 细胞的增殖、迁移、侵袭和上皮-间充质转化（EMT），并激活 NF-κB 信号通路，而 miR-129 抑制则产生相反的效果。此外，SOX4 被鉴定为 miR-129 的直接靶基因。综上所述，本研究结果表明，miR-129 可能通过抑制 CRC 细胞的增殖、迁移、侵袭和 EMT 来发挥肿瘤抑制作用，部分机制可能涉及 NF-κB 信号通路的激活，其作用机制可能是通过靶向 SOX4 mRNA 的 3'非翻译区。
