MicroRNA-16-1-3p Represses Breast Tumor Growth and Metastasis by Inhibiting PGK1-Mediated Warburg Effect.
MicroRNA-16-1-3p Represses Breast Tumor Growth and Metastasis by Inhibiting PGK1-Mediated Warburg Effect.
复制标题
MicroRNA-16-1-3P通过抑制PGK1介导的Warburg效应来抑制乳腺肿瘤的生长和转移。
DOI：
10.3389/fcell.2020.615154
复制
发表时间：
2020
影响因子：
5.5
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Ye T;Liang Y;Zhang D;Zhang X
瓦尔堡效应（有氧糖酵解）是癌症的标志，并正在成为诊断和治疗的一个有前途的目标。磷酸甘油酸激酶1（PGK 1）是有氧糖酵解途径中第一个产生三磷酸腺苷（ATP）的糖酵解酶，在癌症的发生和发展中起着重要作用。然而，microRNAs（miRNAs）如何调节PGK 1介导的有氧糖酵解仍然未知。在这里，我们发现miR-16-1- 3 p通过直接靶向其3′-非翻译区抑制PGK 1表达。通过抑制PGK 1，miR-16-1- 3 p通过降低乳腺癌细胞中的葡萄糖摄取、乳酸和ATP产生、细胞外酸化速率以及增加氧消耗速率来抑制有氧糖酵解。由miR-16-1- 3 p/PGK 1轴调节的有氧糖酵解在体内外调节乳腺癌细胞增殖、迁移、侵袭和转移中至关重要。在乳腺癌患者中，miR-16-1- 3 p表达与PGK 1表达及乳腺癌肺转移呈负相关。我们的研究结果提供了关于miR-16-1- 3 p通过PGK 1抑制在乳腺癌中作为肿瘤抑制因子的作用的线索。通过miR-16-1- 3 p靶向PGK 1可能是乳腺癌治疗的一个有前途的策略。
The Warburg effect (aerobic glycolysis) is a hallmark of cancer and is becoming a promising target for diagnosis and therapy. Phosphoglycerate kinase 1 (PGK1) is the first adenosine triphosphate (ATP)-generating glycolytic enzyme in the aerobic glycolysis pathway and plays an important role in cancer development and progression. However, how microRNAs (miRNAs) regulate PGK1-mediated aerobic glycolysis remains unknown. Here, we show that miR-16-1-3p inhibits PGK1 expression by directly targeting its 3′-untranslated region. Through inhibition of PGK1, miR-16-1-3p suppressed aerobic glycolysis by decreasing glucose uptake, lactate and ATP production, and extracellular acidification rate, and increasing oxygen consumption rate in breast cancer cells. Aerobic glycolysis regulated by the miR-16-1-3p/PGK1 axis is critical for modulating breast cancer cell proliferation, migration, invasion and metastasis in vitro and in vivo. In breast cancer patients, miR-16-1-3p expression is negatively correlated with PGK1 expression and breast cancer lung metastasis. Our findings provide clues regarding the role of miR-16-1-3p as a tumor suppressor in breast cancer through PGK1 suppression. Targeting PGK1 through miR-16-1-3p could be a promising strategy for breast cancer therapy.
登录
查看更多内容
影响因子：
5.2
作者：
Ahmad, Sufian S.;Glatzle, Joerg;Zieker, Derek
通讯作者：
Zieker, Derek
PGK1乙酰化促进肝癌细胞增殖和肿瘤发生
影响因子：
13.5
作者：
Hu, Hongli;Zhu, Wenwei;Gao, Daming
通讯作者：
Gao, Daming
影响因子：
11.5
作者：
Meijer, Tineke W. H.;Kaanders, Johannes H. A. M.;Bussink, Johan
通讯作者：
Bussink, Johan
影响因子：
9.3
作者：
Abdel-Wahab, Ali F.;Mahmoud, Waheed;Al-Harizy, Randa M.
通讯作者：
Al-Harizy, Randa M.
DOI：
10.1007/978-3-030-34025-4_3
发表时间：
2020-01-01
期刊：
TUMOR MICROENVIRONMENT: THE MAIN DRIVER OF METABOLIC ADAPTATION
影响因子：
--
作者：
Pereira-Nunes, Andreia;Afonso, Julieta;Baltazar, Fatima
通讯作者：
Baltazar, Fatima