The malignancy suppression and ferroptosis facilitation of BCL6 in gastric cancer mediated by FZD7 repression are strengthened by RNF180/RhoC pathway.
The malignancy suppression and ferroptosis facilitation of BCL6 in gastric cancer mediated by FZD7 repression are strengthened by RNF180/RhoC pathway.
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RNF 180/RhoC信号通路增强了BCL 6对FZD 7抑制的胃癌恶性抑制和铁凋亡促进作用。
DOI：
10.1186/s13578-023-01020-8
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发表时间：
2023-04-14
影响因子：
7.5
通讯作者：
Yang, Lili
中科院分区：
文献类型：
--
作者：
Guo, Shiwei;Deng, Jingyu;Wang, Pengliang;Kou, Fan;Wu, Zizhen;Zhang, Nannan;Zhao, Zhenzhen;Nie, Yongzhan;Yang, Lili
B细胞淋巴瘤6（BCL 6）是一种转录抑制因子，在多种肿瘤中发挥肿瘤抑制或促进作用。但其在胃癌中的作用及其分子机制尚不清楚。铁凋亡是一种新的细胞程序性死亡，与肿瘤的发生发展密切相关。本研究旨在探讨BCL-6在胃癌恶性进展和铁凋亡中的作用及其机制。首先，通过肿瘤微阵列技术，BCL 6被鉴定为一种重要的生物标志物，它可以减弱GC的增殖和转移，并在GC细胞系中得到证实。通过RNA测序分析BCL 6的下游基因。通过ChIP、双荧光素酶报告基因测定和拯救实验进一步研究了潜在的机制。通过检测细胞死亡率、脂质过氧化反应、丙二醛（MDA）和铁离子（Fe 2+）水平，探讨BCL 6对铁凋亡的影响及其作用机制。采用CHX、MG 132治疗和拯救实验，探讨BCL 6的上游调控机制。我们发现BCL 6在胃癌组织中的表达显著降低，低表达的患者表现出更多的恶性临床特征和不良预后。BCL 6的表达上调可显著抑制胃癌细胞的增殖和转移。另外，我们发现BCL 6直接结合并转录抑制Wnt受体Frizzled 7（FZD 7），从而抑制胃癌细胞的增殖、转移。BCL 6通过FZD 7/β-catenin/TP 63/GPX 4途径促进GC细胞的脂质过氧化、MDA和Fe 2+水平，从而促进GC细胞的铁凋亡。此外，BCL 6在胃癌中的表达和功能受Ring finger protein 180（RNF 180）/ras homolog gene family member C（RhoC）通路的调控，该通路参与了胃癌细胞的增殖和转移。因此，BCL 6可能是一种潜在的中间抑癌基因，可抑制胃癌的恶性进展并诱导铁凋亡，有望成为胃癌发生机制研究的一个有前景的分子生物学标志物。在线版本包含补充材料，可通过10.1186/s13578-023-01020-8获得。
B-cell lymphoma 6 (BCL6) is a transcription repressor that plays a tumor suppressor or promoting role in various tumors. However, its function and molecular mechanism in gastric cancer (GC) remain unclear. Ferroptosis, a novel programmed cell death, is closely related to tumor development. In this research, we aimed to explore the role and mechanism of BCL6 in malignant progression and ferroptosis of gastric cancer. Firstly, BCL6 was identified as an important biomarker that attenuated the proliferation and metastasis of GC through tumor microarrays and confirmed in GC cell lines. RNA sequence was performed to explore the downstream genes of BCL6. The underlying mechanisms were further investigated by ChIP, dual luciferase reporter assays and rescue experiments. Cell death, lipid peroxidation, MDA and Fe2+ level were detected to determine the effect of BCL6 on ferroptosis and the mechanism was revealed. CHX, MG132 treatment and rescue experiments were used to explore the upstream regulatory mechanism of BCL6. Here we showed that BCL6 expression was significantly decreased in GC tissues, and patients with low BCL6 expression showed more malignant clinical features and poor prognosis. The upregulation of BCL6 may significantly inhibited the proliferation and metastasis of GC cells in vitro and in vivo. In addition, we found that BCL6 directly binds and transcriptionally represses Wnt receptor Frizzled 7 (FZD7) to inhibit the proliferation, metastasis of GC cells. We also found that BCL6 promoted lipid peroxidation, MDA and Fe2+ level to facilitate ferroptosis of GC cells by FZD7/β-catenin/TP63/GPX4 pathway. Furthermore, the expression and function of BCL6 in GC were regulated by the ring finger protein 180 (RNF180)/ras homolog gene family member C (RhoC) pathway, which had been elucidated to be involved in significantly mediating the proliferation and metastasis of GC cells. In summary, BCL6 should be considered a potential intermediate tumor suppressor to inhibit the malignant progression and induce ferroptosis, which might be a promising molecular biomarker for further mechanistic investigation of GC. The online version contains supplementary material available at 10.1186/s13578-023-01020-8.
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影响因子：
39.3
作者：
Liu J;Xiao Q;Xiao J;Niu C;Li Y;Zhang X;Zhou Z;Shu G;Yin G
通讯作者：
Yin G
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
16.8
作者：
Choi J;Crotty S
通讯作者：
Crotty S
影响因子：
9.6
作者：
Deng, J.;Liang, H.;Hao, X.
通讯作者：
Hao, X.
影响因子：
4.8
作者：
Liang, Hanyu;Yoo, Si-Eun;Ran, Qitao
通讯作者：
Ran, Qitao