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400016 重庆,重庆医科大学基础医学院细胞生物学与遗传学教研室
[陈俊霞, E-mail: chjunxia@126.comCHEN Junxia, E-mail: chjunxia@126.com
收稿:2021-09-28,
修回:2021-11-07,
纸质出版:2022-04-15
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欧小强, 陈俊霞. 环状RNA circACTN4促进乳腺癌细胞增殖、侵袭和转移的研究[J]. 陆军军医大学学报, 2022,44(7):639-647.
Xiaoqiang OU, Junxia CHEN. Circular RNA circACTN4 promotes proliferation, invasion and metastasis of breast cancer cells[J]. Journal of Army Medical University, 2022, 44(7): 639-647.
欧小强, 陈俊霞. 环状RNA circACTN4促进乳腺癌细胞增殖、侵袭和转移的研究[J]. 陆军军医大学学报, 2022,44(7):639-647. DOI: 10.16016/j.2097-0927.202109206.
Xiaoqiang OU, Junxia CHEN. Circular RNA circACTN4 promotes proliferation, invasion and metastasis of breast cancer cells[J]. Journal of Army Medical University, 2022, 44(7): 639-647. DOI: 10.16016/j.2097-0927.202109206.
目的
2
探讨环状RNA circACTN4(hsa_circ_0050900)在乳腺癌中的表达及其对乳腺癌细胞增殖、侵袭和转移的影响。
方法
2
利用环状RNA芯片分析4对乳腺癌组织和癌旁组织的circRNA表达谱,并用实时荧光定量PCR验证circACTN4的相对表达水平;用circACTN4过表达质粒及对照质粒分别转染乳腺癌细胞MCF-7/MDA-MB-231,采用CCK-8实验、EdU实验、平板克隆实验、细胞划痕实验、Transwell迁移和侵袭实验研究circACTN4在乳腺癌细胞增殖、迁移和侵袭中的作用;Western blot检测circACTN4对CCND1、CCND2和CDK4蛋白表达的影响;在裸鼠体内探讨circACTN4对移植瘤生长转移的影响。
结果
2
CircACTN4在乳腺癌组织中的表达高于癌旁组织(
P
<
0.01),在乳腺癌细胞中的表达高于正常乳腺上皮细胞(
P
<
0.01)。上调circACTN4可增强乳腺癌细胞增殖、迁移和侵袭(
P
<
0.05),提高CCND1、CCND2和CDK4蛋白的表达(
P
<
0.01)。体内实验结果表明:上调circACTN4可促进移植瘤生长与转移,与对照组相比,circACTN4组肿瘤微血管密度显著增加(
P
<
0.05),肺转移结节数量明显增多(
P
<
0.05)。
结论
2
circACTN4在乳腺癌组织和细胞显著高表达,可增强乳腺癌细胞的增殖、迁移和侵袭,并在体内促进移植瘤的生长与转移。
Objective
2
To investigate the expression of circular RNA circACTN4 (also called hsa_circ_0050900) in breast cancer (BC) and its effect on the proliferation
invasion and metastasis of BC cells.
Methods
2
The circRNA expression profiles of 4 pairs of BC tissues and adjacent tissues were analyzed by circRNA chip analysis
and the relative expression level of circACTN4 was detected by qRT-PCR. After BC cell lines MCF-7/MDA-MB-231 were transfected with circACTN4 overexpression plasmid and control plasmid
respectively
the effects of circACTN4 on cell proliferation
migration and invasion were tested by Cell Counting Kit-8 (CCK-8)
EdU assay
colony formation
scratching assay
and Transwell migration and invasion assay. Western blotting was executed to determine the protein expression of CCND1
CCND2 and CDK4. The effects of circACTN4 on the growth and metastasis of transplanted tumors were also observed in nude mice.
Results
2
The expression of circACTN4 was significantly higher in BC tissues and cells than in the paired adjacent tissues and normal breast epithelial cells (
P
<
0.01). Up-regulation of circACTN4 enhanced the proliferation
migration and invasion of BC cells (
P
<
0.05)
and facilitated the expression of CCND1
CCND2 and CDK4 (
P
<
0.01). The results of
in vivo
experiments also showed that up-regulation of circACTN4 promoted the growth and metastasis of transplanted tumors
with the tumor microvascular density and the number of lung metastatic nodules significantly increased in the circACTN4 group
as compared with the control group (
P
<
0.05).
Conclusion
2
circACTN4 is highly expressed in BC tissues and cells. It can promote the proliferation
migration and invasion of BC cells
and facilitate the growth and metastasis of transplanted tumors
in vivo
.
HEER E, HARPER A, ESCANDOR N, et al . Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study[J ] . Lancet Glob Health, 2020, 8(8): e1027-e1037. DOI: 10.1016/S2214-109X(20)30215-1.
ZHAO Z J, SHEN J. Circular RNA participates in the carcinogenesis and the malignant behavior of cancer[J]. RNA Biol, 2017, 14(5): 514-521. DOI: 10.1080/15476286.2015.1122162.
LI Z H, CHEN Z H, HU G H, et al . Roles of circular RNA in breast cancer: present and future[J ] . Am J Transl Res, 2019, 11(7): 3945-3954.
LI Z Y, HUANG C, BAO C, et al . Exon-intron circular RN As regulate transcription in the nucleus[J ] . Nat Struct Mol Biol, 2015, 22(3): 256-264. DOI: 10.1038/nsmb.2959.
ARNAIZ E, SOLE C, MANTEROLA L, et al . CircRNAs and cancer: biomarkers and master regulators[J ] . Semin Cancer Biol, 2019, 58: 90-99. DOI: 10.1016/j.semcancer.2018.12.002.
HE R F, LIU P, XIE X M, et al . circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a[J ] . J Exp Clin Cancer Res, 2017, 36(1): 145. DOI: 10.1186/s13046-017-0614-1.
PATOP I L, WVST S, KADENER S. Past, present, and future of circRNAs[J]. EMBO J, 2019, 38(16): e100836. DOI: 10.15252/embj.2018100836.
VO J N, CIESLIK M, ZHANG Y J, et al . The landscape of circular RNA in cancer[J ] . Cell, 2019, 176(4): 869-881. e13. DOI: 10.1016/j.cell.2018.12.021.
ZENG K X, HE B S, YANG B B, et al . The pro-metastasis effect of circANKS1B in breast cancer[J ] . Mol Cancer, 2018, 17(1): 160. DOI: 10.1186/s12943-018-0914-x.
CAO L L, WANG M, DONG Y J, et al . Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK 2 [J ] . Cell Death Dis, 2020, 11(2): 145. DOI: 10.1038/s41419-020-2336-0..
QU S B, LIU Z C, YANG X S, et al . The emerging functions and roles of circular RNAs in cancer[J ] . Cancer Lett, 2018, 414: 301-309. DOI: 10.1016/j.canlet.2017.11.022.
JACKY LAM W K, DENNIS LO Y M. Circular RNAs as urinary biomarkers[J]. Clin Chem, 2019, 65(10): 1196-1198. DOI: 10.1373/clinchem.2019.309773.
WANG X S, XING L, YANG R, et al . The circACTN 4 interacts with FUBP 1 to promote tumorigenesis and progression of breast cancer by regulating the expression of proto-oncogene MYC[J ] . Mol Cancer, 2021, 20(1): 91. DOI: 10.1186/s12943-021-01383-x..
WILUSZ J E. A 360° view of circular RNAs: From biogenesis to functions[J]. Wiley Interdiscip Rev RNA, 2018, 9(4): e1478. DOI: 10.1002/wrna.1478.
KRISTENSEN L S, ANDERSEN M S, STAGSTED L V W, et al . The biogenesis, biology and cha racterization of circular RNAs[J ] . Nat Rev Genet, 2019, 20(11): 675-691. DOI: 10.1038/s41576-019-0158-7.
JIANG C H, ZENG X H, SHAN R F, et al . The emerging picture of the roles of CircRNA-CDR1as in cancer[J ] . Front Cell Dev Biol, 2020, 8: 590478. DOI: 10.3389/fcell.2020.590478.
PAMUDURTI N R, BARTOK O, JENS M, et al . Translation of circRNAs[J ] . Mol Cell, 2017, 66(1): 9-21. e7. DOI: 10.1016/j.molcel.2017.02.021.
LEI M, ZHENG G T, NING Q Q, et al . Translation and functional roles of circular RNAs in human cancer[J ] . Mol Cancer, 2020, 19(1): 30. DOI: 10.1186/s12943-020-1135-7.
ZHENG X, CHEN L, ZHOU Y, et al . A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling[J ] . Mol Cancer, 2019, 18(1): 47. DOI: 10.1186/s12943-019-1010-6..
DE PALMA M, BIZIATO D, PETROVA T V. Microenvironmental regulation of tumour angiogenesis[J]. Nat RevCancer, 2017, 17(8): 457-474. DOI: 10.1038/nrc.2017.51.
WANG X, XING L, YANG R, et al . The circACTN 4 interacts with FUBP 1 to promote tumorigenesis and progression of breast cancer by regulating the expression of proto-oncogene MYC[J ] . Mol Cancer, 2021, 20(1): 91. DOI: 10.1186/s12943-021-01383-x..
WANG C, YANG Y, ZHANG G, et al . Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis[J ] . Proc Natl Acad Sci USA, 2019, 116(29): 14620-14629. DOI: 10.1073/pnas.1903432116.
HAHM E R, SINGH K B, SINGH S V. C-Myc is a novel target of cell cycle arrest by honokiol in prostate cancer cells[J]. Cell Cycle, 2016, 15(17): 2309-2320. DOI: 10.1080/15384101.2016.1201253.
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