Journal of Shanghai Jiao Tong University (Medical Science) >

2021 , Vol. 41 >Issue 2: 187 - 195

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.02.010

Clinical research

Study on the function and prognosis of circular RNA in colorectal cancer tissues based on high-throughput sequencing

  • Zhong-mao FU ,
  • Zai LUO ,
  • Ze-yin RONG ,
  • Jian-ming ZHANG ,
  • Teng-fei LI ,
  • Zhi-long YU ,
  • Chen HUANG
Expand
  • Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China

Received date: 2020-04-26

  Online published: 2021-02-28

Supported by

National Natural Science Foundation of China(81772526);Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20161425);Shanghai Jiao Tong University Medical Engineering Cross Fund(YG2017MS28);Shanghai Songjiang Science and Technology Project Fund(18SJKJGG23)

Fold

Abstract

Objective

·To reveal the mechanism of colorectal cancer and the association between differential expression of circular RNAs (circRNAs) and patients' prognosis.

Methods

·Colorectal cancer tissues and normal tumor-adjacent tissues were harvested from 12 patients undergoing radical resection of colorectal cancer in the Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, and the expressions of circRNAs were detected by high-throughput sequencing. Function predictions of differentially expressed circRNAs were carried out by gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Two circRNAs were selected from the significantly up-regulated and down-regulated circRNAs respectively, and the accuracy of sequencing results was verified in 44 sets of colorectal cancer tissues by real-time fluorescent quantitative PCR (RT-qPCR). The circRNA-miRNA targeting binding network map was constructed by searching the public database for the four circRNAs. Finally, the relationships between differential expression of circRNAs and prognosis were determined based on the patients' clinical data.

Results

·A total of 20 924 differentially expressed circRNAs were detected after high-throughput sequencing. Compared with normal colorectal tissues, there were 373 circRNAs (︱log2FC︱>1, P<0.05) abnormally and significantly expressed in colorectal cancer tissues, of which 243 were significantly up-regulated and 130 were significantly down-regulated. In 44 pairs of colorectal cancer samples, the results verified by RT-qPCR were basically consistent with the sequencing data. After the circRNA-miRNA-mRNA interactions being plotted, it was found that miRNA and target genes associated with circRNA may play an important role in the pathogenesis of colorectal cancer. Combined with the prognosis information, the patients with high expression of hsa_circ_0023984 or hsa_circ_0008192 had poorer prognosis while patients with high expression of hsa_circ_0020093 or hsa_circ_0069922 had better prognosis.

Conclusion

·Abnormally expressed circRNAs in colorectal cancer tissues lay a foundation for further studies on the occurrence and development of colorectal cancer, and provide valuable information for the development of new clinical diagnostic markers and treatments in the future.

Key words： colorectal cancer; circular RNA (circRNA); prognosis; regulatory network

Cite this article

Zhong-mao FU , Zai LUO , Ze-yin RONG , Jian-ming ZHANG , Teng-fei LI , Zhi-long YU , Chen HUANG . Study on the function and prognosis of circular RNA in colorectal cancer tissues based on high-throughput sequencing[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(2) : 187 -195 . DOI: 10.3969/j.issn.1674-8115.2021.02.010

References

1 Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
2 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30.
3 Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
4 Zhang H, Wang Z, Ma R, et al. MicroRNAs as biomarkers for the progression and prognosis of colon carcinoma[J]. Int J Mol Med, 2018, 42(4): 2080-2088.
5 Sun K, Han RJ, Han Y, et al. Accuracy of combined computed tomography colonography and dual energy iiodine map imaging for detecting colorectal masses using high-pitch dual-source CT[J]. Sci Rep, 2018, 8(1): 3790.
6 Thomsen M, Skovlund E, Sorbye H, et al. Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome[J]. Br J Cancer, 2018, 118(12): 1609-1616.
7 Gao Y, Wang J, Zhou Y, et al. Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer[J]. Sci Rep, 2018, 8(1): 2732.
8 Chen LL, Yang L. Regulation of circRNA biogenesis[J]. RNA Biol, 2015, 12(4): 381-388.
9 Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency[J]. Nature, 2013, 495(7441): 333-338.
10 Pamudurti NR, Bartok O, Jens M, et al. Translation of circRNAs[J]. Mol Cell, 2017, 66(1): 9-21.e7.
11 Barrett SP, Salzman J. Circular RNAs: analysis, expression and potential functions[J]. Dev Camb Engl, 2016, 143(11): 1838-1847.
12 Zhu Z, Rong Z, Luo Z, et al. Circular RNA circNHSL1 promotes gastric cancer progression through the miR-1306-3p/SIX1/vimentin axis[J]. Mol Cancer, 2019, 18(1): 126.
13 Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3): 145-164.
14 Wang Y, Wang Z. Efficient backsplicing produces translatable circular mRNAs[J]. RNA, 2015, 21(2): 172-179.
15 Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats[J]. RNA, 2013, 19(2): 141-157.
16 Schwanh?usser B, Busse D, Li N, et al. Global quantification of mammalian gene expression control[J]. Nature, 2011, 473(7347): 337-342.
17 Vo JN, Cieslik M, Zhang YJ, et al. The landscape of circular RNA in cancer[J]. Cell, 2019, 176(4): 869-881.e13.
18 Zhu Z, Yu Z, Rong Z, et al. The novel GINS4 axis promotes gastric cancer growth and progression by activating Rac1 and CDC42[J]. Theranostics, 2019, 9(26): 8294-8311.
19 Li Y, Zheng QP, Bao CY, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis[J]. Cell Res, 2015, 25(8): 981-984.
20 Zhu P, Zhu X, Wu J, et al. IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3[J]. Nat Immunol, 2019, 20(2): 183-194.
21 Li WL, Xu YQ, Wang XD, et al. circCCT3 modulates vascular endothelial growth factor A and Wnt signaling to enhance colorectal cancer metastasis through sponging miR-613[J]. DNA Cell Biol, 2020, 39(1): 118-125.
22 Zhong Z, Huang M, Lv M, et al. Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer progression through modulating VEGFA/VEGFR2 signaling pathway[J]. Cancer Lett, 2017, 403: 305-317.
23 Liang WC, Wong CW, Liang PP, et al. Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway[J]. Genome Biol, 2019, 20(1): 84.
24 Zhi X, Zhang J, Cheng Z, et al. circLgr4 drives colorectal tumorigenesis and invasion through Lgr4-targeting peptide[J]. Int J Cancer, 2019. DOI:10.1002/ijc.32549.
25 Rong DW, Sun HD, Li ZX, et al. An emerging function of circRNA-miRNAs-mRNA axis in human diseases[J]. Oncotarget, 2017, 8(42): 73271-73281.
26 Gallí M, van Gool F, Rongvaux A, et al. The nicotinamide phosphoribosyltransferase: a molecular link between metabolism, inflammation, and cancer[J]. Cancer Res, 2010, 70(1): 8-11.
27 Garten A, Schuster S, Penke M, et al. Physiological and pathophysiological roles of NAMPT and NAD metabolism[J]. Nat Rev Endocrinol, 2015, 11(9): 535-546.
28 Sampath D, Zabka TS, Misner DL, et al. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer[J]. Pharmacol Ther, 2015, 151: 16-31.
29 Lucena-Cacace A, Otero-Albiol D, Jiménez-García MP, et al. NAMPT is a potent oncogene in colon cancer progression that modulates cancer stem cell properties and resistance to therapy through Sirt1 and PARP[J]. Clin Cancer Res, 2018, 24(5): 1202-1215.
Options
Outlines

/

〈 〉