Circular RNA Hsa_circ_0064559 Affects Tumor Cell Growth and Progression of Colorectal Cancer

Overview

Journal World J Surg Oncol

Publisher Biomed Central

Specialties General Surgery
Oncology

Date 2023 Jun 6

PMID 37280630

Authors

Yanan Zhen

Guodong Sun

Cunbao Chen

Jianqi Li

Ruixue Xiao

Zhongfa Xu

Affiliations

Soon will be listed here.

Abstract

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. It is essential to identify new CRC-associated therapeutic targets and diagnostic biomarkers. Previous studies have demonstrated that a series of circular RNAs (circRNAs) play a crucial role in CRC pathogenesis. This study assessed the potential of hsa_circ_0064559 in tumor cell growth and progression of CRC.

Methods: Six pairs of matched CRC and normal colorectal tissue samples were sequenced using the Affymetrix Clariom D array. Using RNA interference, the expression of thirteen circRNAs was knocked down in CRC cells. The proliferation of CRC cell lines (RKO and SW620 cells) was detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were determined by flow-cytometric analysis. An in vivo study uses nude mice to establish a CRC mouse model. The differentially expressed genes were analyzed using Affymetrix primeview human GeneChip array and verified by polymerase chain reaction.

Results: Affymetrix Clariom D array analysis revealed that thirteen circRNAs were upregulated in CRC. The proliferation of CRC cell lines was decreased, while the proportion of apoptotic and G1 phase cells was higher after hsa_circ_0064559 knockdown. In vivo xenograft nude mice model revealed that the volume and weight of the tumor were reduced by hsa_circ_0064559 knockdown. In Affymetrix primeview human GeneChip array, we found six upregulated genes (STAT1, ATF2, TNFRSF10B, TGFBR2, BAX, and SQSTM1) and two downregulated genes (SLC4A7 and CD274) related to apoptosis and proliferation of colorectal cancer cells after hsa_circ_0064559 knockdown.

Conclusions: The hsa_circ_0064559 knockdown could inhibit the proliferation, promote apoptosis in CRC cell lines in vitro, and inhibit the development of CRC tumors in vivo. The mechanism may be related to activating a wide range of signaling pathways. The hsa_circ_0064559 may be a potential biomarker for early diagnosis or prognosis of CRC and a novel drug target for CRC therapy.

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References

Gothai S, Muniandy K, Gnanaraj C, Ibrahim I, Shahzad N, Al-Ghamdi S . Pharmacological insights into antioxidants against colorectal cancer: A detailed review of the possible mechanisms. Biomed Pharmacother. 2018; 107:1514-1522. DOI: 10.1016/j.biopha.2018.08.112. View

Li J, Liang H, Bai M, Ning T, Wang C, Fan Q . miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer. PLoS One. 2015; 10(6):e0130194. PMC: 4462589. DOI: 10.1371/journal.pone.0130194. View

Lee I, Shiroma E, Lobelo F, Puska P, Blair S, Katzmarzyk P . Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012; 380(9838):219-29. PMC: 3645500. DOI: 10.1016/S0140-6736(12)61031-9. View

Sayad A, Najafi S, Hussen B, Jamali E, Taheri M, Ghafouri-Fard S . The role of circular RNAs in pancreatic cancer: new players in tumorigenesis and potential biomarkers. Pathol Res Pract. 2022; 232:153833. DOI: 10.1016/j.prp.2022.153833. View

Li X, Wang Z, Ye C, Zhao B, Li Z, Yang Y . RNA sequencing reveals the expression profiles of circRNA and indicates that circDDX17 acts as a tumor suppressor in colorectal cancer. J Exp Clin Cancer Res. 2018; 37(1):325. PMC: 6307166. DOI: 10.1186/s13046-018-1006-x. View

Zhang L, Cao F, Zhang G, Shi L, Chen S, Zhang Z . Trends in and Predictions of Colorectal Cancer Incidence and Mortality in China From 1990 to 2025. Front Oncol. 2019; 9:98. PMC: 6393365. DOI: 10.3389/fonc.2019.00098. View

Jin H, Seo G, Lee S . Isoliquiritigenin-mediated p62/SQSTM1 induction regulates apoptotic potential through attenuation of caspase-8 activation in colorectal cancer cells. Eur J Pharmacol. 2018; 841:90-97. DOI: 10.1016/j.ejphar.2018.10.015. View

Totten S, Im Y, Cepeda Canedo E, Najyb O, Nguyen A, Hebert S . STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer. Nat Commun. 2021; 12(1):3299. PMC: 8175605. DOI: 10.1038/s41467-021-23396-2. View

Dashti S, Buchanan D, Jayasekara H, Ait Ouakrim D, Clendenning M, Rosty C . Alcohol Consumption and the Risk of Colorectal Cancer for Mismatch Repair Gene Mutation Carriers. Cancer Epidemiol Biomarkers Prev. 2016; 26(3):366-375. PMC: 5336397. DOI: 10.1158/1055-9965.EPI-16-0496. View

10.

Ruan J . A robust circular RNA-based prognostic signature for postoperative recurrence in stage II/III colon cancer. AIMS Genet. 2020; 6(4):67-69. PMC: 6949465. DOI: 10.3934/genet.2019.4.67. View

11.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

12.

Chen S, Shen X . Long noncoding RNAs: functions and mechanisms in colon cancer. Mol Cancer. 2020; 19(1):167. PMC: 7697375. DOI: 10.1186/s12943-020-01287-2. View

13.

Akhter R . Circular RNA and Alzheimer's Disease. Adv Exp Med Biol. 2018; 1087:239-243. DOI: 10.1007/978-981-13-1426-1_19. View

14.

Bardou M, Barkun A, Martel M . Obesity and colorectal cancer. Gut. 2013; 62(6):933-47. DOI: 10.1136/gutjnl-2013-304701. View

15.

Jian X, He H, Zhu J, Zhang Q, Zheng Z, Liang X . Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340. Mol Cancer. 2020; 19(1):20. PMC: 6993513. DOI: 10.1186/s12943-020-1134-8. View

16.

Yang H, Zhang H, Yang Y, Wang X, Deng T, Liu R . Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis. Theranostics. 2020; 10(18):8211-8226. PMC: 7381736. DOI: 10.7150/thno.44419. View

17.

Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T . CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis. 2018; 9(4):417. PMC: 5856798. DOI: 10.1038/s41419-018-0454-8. View

18.

Yang L, Sun H, Liu X, Chen J, Tian Z, Xu J . Circular RNA hsa_circ_0004277 contributes to malignant phenotype of colorectal cancer by sponging miR-512-5p to upregulate the expression of PTMA. J Cell Physiol. 2020; . DOI: 10.1002/jcp.29484. View

19.

Yang G, Wang Y, Zeng Y, Gao G, Liang X, Zhou M . Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet. 2013; 381(9882):1987-2015. PMC: 7159289. DOI: 10.1016/S0140-6736(13)61097-1. View

20.

Ji W, Qiu C, Wang M, Mao N, Wu S, Dai Y . Hsa_circ_0001649: A circular RNA and potential novel biomarker for colorectal cancer. Biochem Biophys Res Commun. 2018; 497(1):122-126. DOI: 10.1016/j.bbrc.2018.02.036. View