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沉默RIF1可降低人宫颈癌细胞的生长、迁移能力，并增加其对顺铂的敏感性。

Silencing RIF1 decreases cell growth, migration and increases cisplatin sensitivity of human cervical cancer cells.

作者信息

Mei Ying, Peng Chen, Liu Yong-Bin, Wang Jing, Zhou Hong-Hao

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.

Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.

出版信息

Oncotarget. 2017 Nov 6;8(63):107044-107051. doi: 10.18632/oncotarget.22315. eCollection 2017 Dec 5.

DOI:10.18632/oncotarget.22315
PMID:29291010
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5739795/
Abstract

Replication timing regulatory factor 1 (RIF1) plays an important role in DNA replication regulation, stem cell pluripotency and DNA repair pathway. However, little is known about the molecular mechanisms and physiological significance of RIF1 in cancer and chemotherapy efficacy. In this study, we found that RIF1 is upregulated in cervical cancer tissues compared with normal tissues both at mRNA and protein levels through online databases. RIF1 knockdown reduced cervical cancer cell growth, colony formation, migration and epithelial-mesenchymal transition (EMT) markers. Flow cytometry analysis indicated that RIF1 knockdown induced apoptosis and G2 cell cycle arrest. Furthermore, RIF1 knockdown increased cisplatin sensitivity, cisplatin-induced G2/M phase arrest, apoptosis and led to defects in DNA repair in a concentration-dependent manner. In terms of mechanism research, increased CDKN1A expression and Bax/Bcl-2/caspase-3 signaling pathway might be involved in the G2/M phase arrest and increased apoptosis in RIF1-silenced cervical cancer cells. Thus, these findings indicate that RIF1 knockdown prior to chemotherapy may be a potential effective therapeutic strategy for cervical cancer.

摘要

复制时间调控因子1（RIF1）在DNA复制调控、干细胞多能性和DNA修复途径中发挥着重要作用。然而，关于RIF1在癌症及化疗疗效中的分子机制和生理意义，人们所知甚少。在本研究中，我们通过在线数据库发现，与正常组织相比，RIF1在宫颈癌组织中的mRNA和蛋白质水平均上调。RIF1敲低可降低宫颈癌细胞的生长、集落形成、迁移以及上皮-间质转化（EMT）标志物。流式细胞术分析表明，RIF1敲低可诱导细胞凋亡和G2期细胞周期阻滞。此外，RIF1敲低以浓度依赖的方式增加了顺铂敏感性、顺铂诱导的G2/M期阻滞、细胞凋亡，并导致DNA修复缺陷。在机制研究方面，CDKN1A表达增加以及Bax/Bcl-2/caspase-3信号通路可能参与了RIF1沉默的宫颈癌细胞中的G2/M期阻滞和细胞凋亡增加。因此，这些发现表明化疗前敲低RIF1可能是一种潜在有效的宫颈癌治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/e2e13a8c5dd3/oncotarget-08-107044-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/a3b2055c9c96/oncotarget-08-107044-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/1bb191706c9b/oncotarget-08-107044-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/7bfe1144de39/oncotarget-08-107044-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/d333e6292d0d/oncotarget-08-107044-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/e2e13a8c5dd3/oncotarget-08-107044-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/a3b2055c9c96/oncotarget-08-107044-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/1bb191706c9b/oncotarget-08-107044-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/7bfe1144de39/oncotarget-08-107044-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/d333e6292d0d/oncotarget-08-107044-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/5739795/e2e13a8c5dd3/oncotarget-08-107044-g005.jpg

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引用本文的文献

[1]
Dysregulated Alternative Splicing in Breast Cancer Subtypes of RIF1 and Other Transcripts.

Int J Mol Sci. 2025-7-29

[2]
Shedding Light on the Interaction Between Rif1 and Telomeres in Ovarian Cancer.

Aging Dis. 2024-4-1

[3]
Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets.

Cancers (Basel). 2022-12-18

[4]
Somatic structural variant formation is guided by and influences genome architecture.

Genome Res. 2022-4

[5]
SPR Analysis of SUMO-Murine Rap1-Interacting Factor 1 C-Terminal Domain Interaction with G4.

Biosensors (Basel). 2022-1-12

[6]
Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.

Int J Mol Sci. 2020-6-3

[7]
Scorpion Venom Induces Apoptosis in Cervical Cancer Cell Lines.

Evid Based Complement Alternat Med. 2019-6-23

[8]
Single‑cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer.

Oncol Rep. 2019-4-15

[9]
Effect of RIF1 on response of non-small-cell lung cancer patients to platinum-based chemotherapy by regulating MYC signaling pathway.

Int J Biol Sci. 2018-10-20

[10]
RIF1 promotes tumor growth and cancer stem cell-like traits in NSCLC by protein phosphatase 1-mediated activation of Wnt/β-catenin signaling.

Cell Death Dis. 2018-9-20

本文引用的文献

[1]
BMX/Etk promotes cell proliferation and tumorigenicity of cervical cancer cells through PI3K/AKT/mTOR and STAT3 pathways.

Oncotarget. 2017-7-25

[2]
Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin.

Arch Biochem Biophys. 2017-6-1

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S100A7 promotes the migration, invasion and metastasis of human cervical cancer cells through epithelial-mesenchymal transition.

Oncotarget. 2017-4-11

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Oncotarget. 2017-3-14

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Clin Cancer Res. 2017-2-15

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Mol Cell. 2016-1-21

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Nat Struct Mol Biol. 2015-10-5

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