ALDH6A1 通过调节癌细胞系中的 RAS/RAF/MEK/ERK 通路来减弱结肠癌的进展。
ALDH6A1 weakens the progression of colon cancer via modulating the RAS/RAF/MEK/ERK pathway in cancer cell lines.
机构信息
The Second Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, China.
The Tenth Department of Proctology Department, Dalian University Affiliated Xinhua Hospital, China.
出版信息
Gene. 2022 Oct 30;842:146757. doi: 10.1016/j.gene.2022.146757. Epub 2022 Jul 27.
BACKGROUND
Aldehyde dehydrogenase 6 family member A1 (ALDH6A1) is associated with multiple diseases, but its pathogenesis in colon cancer (CC) is ambiguous and needs further study so that this research explores the function of ALDH6A1 in CC.
METHODS
The level of ALDH6A1 in colon adenocarcinoma (COAD), CC tissues, and cells was measured by starBase v2.0, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. Post transfection with overexpressed (oe)-ALDH6A1, cell biological behaviors, as well as apoptosis-, matrix metalloproteinase (MMP)-, and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway-related markers were measured by cell function experiments, qRT-PCR, and western blot. Next, the effects of small interfering RNA targeting ALDH6A1 (si-ALDH6A1) and RAS/RAF inhibitor (MCP110) on cell biological behaviors, as well as apoptosis-, MMP-, and RAS/RAF/MEK/ERK pathway-related markers were detected again.
RESULTS
ALDH6A1 was low-expressed in COAD, CC tissues, and cells. Oe-ALDH6A1 weakened cell vitality, migration and invasionbut facilitated apoptosis; while it reduced expression levels of Bcl-2, MMP-2, MMP-9 and the RAS/RAF/MEK/ERK pathway-related markers but promoted Bax level. However, the regulation of si-ALDH6A1 on cell biological behaviors and related genes was opposite to that of oe-ALDH6A1. Moreover, MCP110 rescued the regulation of si-ALDH6A1 on cell biological behaviors, expressions of apoptosis- MMP- as well as RAS/RAF/MEK/ERK pathway-related markers. To sum up, ALDH6A1 attenuated CC progression by down-regulating the expressions of RAS/RAF/MEK/ERK pathway-related markers.
背景
醛脱氢酶 6 家族成员 A1（ALDH6A1）与多种疾病相关，但在结肠癌（CC）中的发病机制尚不清楚，需要进一步研究，因此本研究探讨了 ALDH6A1 在 CC 中的功能。
方法
通过 starBase v2.0、实时定量聚合酶链反应（qRT-PCR）和蛋白质印迹法测定结肠腺癌（COAD）、CC 组织和细胞中 ALDH6A1 的水平。转染过表达（oe）-ALDH6A1 后，通过细胞功能实验、qRT-PCR 和蛋白质印迹法测定细胞生物学行为以及凋亡、基质金属蛋白酶（MMP）和大鼠肉瘤病毒（RAS）/快速加速纤维肉瘤（RAF）/丝裂原激活蛋白激酶（MEK）/细胞外信号调节激酶（ERK）通路相关标志物。然后，再次检测针对 ALDH6A1 的小干扰 RNA（si-ALDH6A1）和 RAS/RAF 抑制剂（MCP110）对细胞生物学行为以及凋亡、MMP 和 RAS/RAF/MEK/ERK 通路相关标志物的影响。
结果
ALDH6A1 在 COAD、CC 组织和细胞中低表达。oe-ALDH6A1 减弱细胞活力、迁移和侵袭，但促进细胞凋亡；同时降低 Bcl-2、MMP-2、MMP-9 和 RAS/RAF/MEK/ERK 通路相关标志物的表达水平，而促进 Bax 水平。然而，si-ALDH6A1 对细胞生物学行为和相关基因的调节与 oe-ALDH6A1 相反。此外，MCP110 挽救了 si-ALDH6A1 对细胞生物学行为、凋亡、MMP 以及 RAS/RAF/MEK/ERK 通路相关标志物表达的调节。总之，ALDH6A1 通过下调 RAS/RAF/MEK/ERK 通路相关标志物的表达来减弱 CC 的进展。
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