PGM5P3-AS1 通过调控 MAP1LC3C 促进细胞铁死亡从而抑制三阴性乳腺癌的恶性进展。
PGM5P3-AS1 regulates MAP1LC3C to promote cell ferroptosis and thus inhibiting the malignant progression of triple-negative breast cancer.
机构信息
Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
出版信息
Breast Cancer Res Treat. 2022 Jun;193(2):305-318. doi: 10.1007/s10549-021-06501-3. Epub 2022 Mar 24.
PURPOSE
Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer characteristic of high recurrence rate and poor prognosis. According to previous studies and bioinformatics prediction, PGM5P3-AS1 has been found to be significantly down-regulated in TNBC cells. In addition, cell ferroptosis has become a hotspot in breast cancer research and TNBC has been reported to be more sensitive to ferroptosis than receptor positive breast cancer. Hence, we aim at exploring the molecular mechanism of PGM5P3-AS1 in TNBC cells and further explore whether PGM5P3-AS1 can inhibit TNBC progression via promoting cell ferroptosis.
METHODS
The expression of genes in TNBC cells was verified by RT-qPCR assay. Functional assays were taken to evaluate the impact PGM5P3-AS1 may exert on TNBC progression. The regulatory pattern of PGM5P3-AS1 on cell ferroptosis in TNBC was validated through mechanism assays.
RESULTS
PGM5P3-AS1 was proved to be down-regulated in TNBC cells and suppressed TNBC cell proliferation as well as migration. PGM5P3-AS1 promoted cell ferroptosis in TNBC by recruiting RNA-binding protein (RBP) NOP58 to stabilize MAP1LC3C mRNA, and thus inhibiting TNBC progression.
CONCLUSION
PGM5P3-AS1 regulated MAP1LC3C to promote cell ferroptosis and thus inhibiting the malignant progression of TNBC.
目的
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，其特点是复发率高、预后差。根据先前的研究和生物信息学预测，PGM5P3-AS1 在 TNBC 细胞中显著下调。此外，细胞铁死亡已成为乳腺癌研究的热点，并且已经报道 TNBC 比受体阳性乳腺癌对铁死亡更敏感。因此，我们旨在探讨 PGM5P3-AS1 在 TNBC 细胞中的分子机制，并进一步探讨 PGM5P3-AS1 是否可以通过促进细胞铁死亡来抑制 TNBC 的进展。
方法
通过 RT-qPCR 检测 TNBC 细胞中基因的表达。通过功能测定评估 PGM5P3-AS1 对 TNBC 进展可能产生的影响。通过机制测定验证 PGM5P3-AS1 对 TNBC 细胞铁死亡的调节模式。
结果
PGM5P3-AS1 在 TNBC 细胞中下调，并抑制 TNBC 细胞的增殖和迁移。PGM5P3-AS1 通过招募 RNA 结合蛋白（RBP）NOP58 稳定 MAP1LC3C mRNA，从而促进 TNBC 细胞铁死亡，从而抑制 TNBC 的进展。
结论
PGM5P3-AS1 通过调节 MAP1LC3C 促进细胞铁死亡，从而抑制 TNBC 的恶性进展。
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