Regulation of Circular RNA CircNFATC3 in Cancer Cells Alters Proliferation, Migration, and Oxidative Phosphorylation.

Regulation of Circular RNA CircNFATC3 in Cancer Cells Alters Proliferation, Migration, and Oxidative Phosphorylation.
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癌细胞中圆形RNA CircnFATC3的调节改变了增殖,迁移和氧化磷酸化。

DOI:
10.3389/fcell.2021.595156
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发表时间:
2021
影响因子:
5.5
通讯作者:
Malek JA
Malek JA
中科院分区:
生物学2区
文献类型:
--
作者:
Karedath T;Al-Dasim FM;Ahmed I;Al-Qurashi A;Raza A;Andrews SS;Ahmed AA;Ali Mohamoud Y;Dermime S;Malek JA

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环状RNA曾经被认为是转录组测序的产物,但最近被鉴定为在不同类型的癌症中具有功能相关性。尽管仍然没有明确的circRNA的主要功能,但几项研究已经揭示了circRNA在各种真核生物中以调节的方式表达,通常不依赖于其亲本线性同种型,表明跨物种的保守性。在实体瘤的转录组数据中鉴定了来自NFATC 3的外显子2和3的丰富且未表征的环状RNA circNFATC 3。在这里,我们表明,在乳腺癌和卵巢癌细胞系中使用RNAi介导的circRNA沉默和环状迷你载体介导的环状结构过表达的circNFATC 3功能获得和丧失实验影响分子表型。circNFATC 3的敲低诱导细胞增殖、侵袭、迁移和氧化磷酸化的减少。MDA-MB-231和SK-0 V-3细胞中circNFATC 3的功能获得显示细胞增殖、迁移和呼吸的显著增加。上述结果表明,circNFATC 3是乳腺癌和卵巢癌中功能相关的环状RNA。
Circular RNAs were once considered artifacts of transcriptome sequencing but have recently been identified as functionally relevant in different types of cancer. Although there is still no clear main function of circRNAs, several studies have revealed that circRNAs are expressed in various eukaryotic organisms in a regulated manner often independent of their parental linear isoforms demonstrating conservation across species. circNFATC3, an abundant and uncharacterized circular RNA of exon 2 and 3 from NFATC3, was identified in transcriptomic data of solid tumors. Here we show that circNFATC3 gain- and loss-of-function experiments using RNAi-mediated circRNA silencing and circular mini vector-mediated overexpression of circularized constructs in breast and ovarian cancer cell lines affect molecular phenotypes. The knockdown of circNFATC3 induces a reduction in cell proliferation, invasion, migration, and oxidative phosphorylation. Gain-of-function of circNFATC3 in MDA-MB-231 and SK-OV-3 cells show a significant increase in cell proliferation, migration, and respiration. The above results suggest that circNFATC3 is a functionally relevant circular RNA in breast and ovarian cancer.
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