Research status and prospect of circular RNA in pancreatic cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Songsong ¹ , FU Wen ² , XIE Fuming ² ,  WANG Huaizhi ²

1. Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P. R. China;
2. Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400013, P. R. China;

Corresponding?author：

WANG Huaizhi, Email: whuaizhi@gmail.com

Keywords：

circular RNA; pancreatic cancer; biomarker

DOI：

10.7507/1007-9424.202011004

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To understand the research status and future directions of circular RNA (circRNA) in pancreatic cancer, and to provide references for its further research.Method The recent literatures on studies of the role of circRNA in the pancreatic cancer were reviewed.Results The retsults of high-throughput sequencing had shown that large amounts of circRNA expressed abnormally in the pancreatic cancer tissues and pancreatic cancer cell lines, and they participated in the occurrence and development of pancreatic cancer, drug resistance, autophagy, and immune escape by regulating downstream target molecules such as microRNA or RNA-binding protein.Conclusion Certain circRNAs with important function are expected to become biomarkers for early diagnosis of pancreatic cancer and molecular targets for treatment, so as to achieve goals of early diagnosis and targeted therapy of pancreatic cancer.

Citation： LIU Songsong, FU Wen, XIE Fuming, WANG Huaizhi. Research status and prospect of circular RNA in pancreatic cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(1): 18-22. doi: 10.7507/1007-9424.202011004 Copy

1.	中國抗癌協會胰腺癌專業委員會. 胰腺癌綜合診治指南(2018版). 臨床肝膽病雜志, 2018, 34(10): 2109-2120.
2.	Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res, 2014, 74(11): 2913-2921.
3.	Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14(CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125): 1023-1075.
4.	Xu Z, Shen J, Hua S, et al. High-throughput sequencing of circRNAs reveals novel insights into mechanisms of nigericin in pancreatic cancer. BMC Genomics, 2019, 20(1): 716.
5.	Li J, Li Z, Jiang P, et al. Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis. J Exp Clin Cancer Res, 2018, 37(1): 177.
6.	Li ZH, WU YF, Li J, et al. Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer. Cancer Lett, 2018, 432: 237-250.
7.	Arnberg AC, Van Ommen GJ, Grivell LA, et al. Some yeast mitochondrial RNAs are circular. Cell, 1980, 19(2): 313-319.
8.	程龍, 王攀. circRNA的功能及其與胃癌關系的研究進展. 中國普外基礎與臨床雜志, 2019, 26(7): 892-896.
9.	Zheng QP, Bao CY, Guo WJ, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun, 2016, 7: 11215.
10.	杜公博, 殷德濤. 環狀RNA在甲狀腺乳頭狀癌中的研究進展. 中國普外基礎與臨床雜志, 2020, 27(7): 890-894.
11.	Haque S, Harries L W. Circular RNAs (circRNAs) in health and disease. Genes (Basel), 2017, 8(12): 353.
12.	Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature, 2013, 495(7441): 384-388.
13.	Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 2013, 495(7441): 333-338.
14.	Liu L, Liu FB, Huang M, et al. Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway. Hepatobiliary Pancreat Dis Int, 2019, 18(6): 580-586.
15.	Jiang PC, Bu SR. Clinical value of circular RNAs and autophagy-related miRNAs in the diagnosis and treatment of pancreatic cancer. Hepatobiliary Pancreat Dis Int, 2019, 18(6): 511-516.
16.	Du WW, Yang W, Liu E, et al. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res, 2016, 44(6): 2846-2858.
17.	Li Q, Wang Y, Wu S, et al. CircACC1 regulates assembly and activation of AMPK complex under metabolic stress. Cell Metab, 2019, 30(1): 157-173.
18.	McGlynn L M, McCluney S, Jamieson N B, et al. SIRT3 & SIRT7: potential novel biomarkers for determining outcome in pancreatic cancer patients. PLoS One, 2015, 10(6): e0131344.
19.	Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell, 2013, 51(6): 792-806.
20.	Hansen TB, Wiklund ED, Bramsen JB, et al. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J, 2011, 30(21): 4414-4422.
21.	Ng WL, Marinov GK, Liau ES, et al. Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway. RNA Biol, 2016, 13(9): 861-871.
22.	Chen RX, Chen X, Xia LP, et al. N⁶-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun, 2019, 10(1): 4695.
23.	Tatomer DC, Wilusz JE. An unchartered journey for ribosomes: circumnavigating circular RNAs to produce proteins. Mol Cell, 2017, 66(1): 1-2.
24.	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. Genome Biol, 2019, 20(1): 84.
25.	Wang J, Zhu S, Meng N, et al. ncRNA-encoded peptides or proteins and cancer. Mol Ther, 2019, 27(10): 1718-1725.
26.	Guo S, Xu X, Ouyang Y, et al. Microarray expression profile analysis of circular RNAs in pancreatic cancer. Mol Med Rep, 2018, 17(6): 7661-7671.
27.	Yang F, Liu DY, Guo JT, et al. Circular RNA circ-LDLRAD3 as a biomarker in diagnosis of pancreatic cancer. World J Gastroenterol, 2017, 23(47): 8345-8354.
28.	王赫, 劉冬妍, 王晟, 等. 環狀RNA hsa-circ-0015022作為胰腺癌新型診斷生物標志物研究. 臨床軍醫雜志, 2020, 48(1): 30-34.
29.	Whiteside TL. The effect of tumor-derived exosomes on immune regulation and cancer immunotherapy. Future Oncol, 2017, 13(28): 2583-2592.
30.	Li Y, Zheng Q, Bao C, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res, 2015, 25(8): 981-984.
31.	An Y, Cai H, Zhang Y, et al. circZMYM2 competed endogenously with miR-335-5p to regulate JMJD2C in pancreatic cancer. Cell Physiol Biochem, 2018, 51(5): 2224-2236.
32.	Wong CH, Lou UK, Li Y, et al. CircFOXK2 promotes growth and metastasis of pancreatic ductal adenocarcinoma by complexing with RNA-binding proteins and sponging miR-942. Cancer Res, 2020, 80(11): 2138-2149.
33.	Guo X, Zhou Q, Su D, et al. Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis. Mol Cancer, 2020, 19(1): 83.
34.	Kong Y, Li Y, Luo Y, et al. circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer. Mol Cancer, 2020, 19(1): 82.
35.	Gong R, Jiang Y. Non-coding RNAs in pancreatic ductal adenocarcinoma. Front Oncol, 2020, 10: 309.
36.	Shi H, Li H, Zhen T, et al. hsa_circ_001653 Implicates in the development of pancreatic ductal adenocarcinoma by regulating microRNA-377-mediated HOXC6 axis. Mol Ther Nucleic Acids, 2020, 20: 252-264.
37.	Yang J, Cong X, Ren M, et al. Circular RNA hsa_circRNA_0007334 is predicted to promote MMP7 and COL1A1 expression by functioning as a miRNA sponge in pancreatic ductal adenocarcinoma. J Oncol, 2019, 2019: 7630894.
38.	Xing C, Ye H, Wang W, et al. Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression. Artif Cells Nanomed Biotechnol, 2019, 47(1): 3920-3928.
39.	Liu Y, Xia L, Dong L, et al. CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by sponging miR-330-5p and targets RASSF1. Cancer Manag Res, 2020, 12: 921-929.
40.	Huang WJ, Wang Y, Liu S, et al. Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression. Cancer Lett, 2018, 422: 70-80.
41.	Xu C, Yu Y, Ding F. Microarray analysis of circular RNA expression profiles associated with gemcitabine resistance in pancreatic cancer cells. Oncol Rep, 2018, 40(1): 395-404.
42.	Shao F, Huang M, Meng F, et al. Circular RNA signature predicts gemcitabine resistance of pancreatic ductal adenocarcinoma. Front Pharmacol, 2018, 9: 584.
43.	Li H, Hao X, Wang H, et al. Circular RNA expression profile of pancreatic ductal adenocarcinoma revealed by microarray. Cell Physiol Biochem, 2016, 40(6): 1334-1344.
44.	Takiuchi D, Eguchi H, Nagano H, et al. Involvement of microRNA-181b in the gemcitabine resistance of pancreatic cancer cells. Pancreatology, 2013, 13(5): 517-523.
45.	Yang MC, Wang HC, Hou YC, et al. Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine. Mol Cancer, 2015, 14: 179.
46.	Wei DM, Jiang MT, Lin P, et al. Potential ceRNA networks involved in autophagy suppression of pancreatic cancer caused by chloroquine diphosphate: A study based on differentially-expressed circRNAs, lncRNAs, miRNAs and mRNAs. Int J Oncol, 2019, 54(2): 600-626.

1. 中國抗癌協會胰腺癌專業委員會. 胰腺癌綜合診治指南(2018版). 臨床肝膽病雜志, 2018, 34(10): 2109-2120.
2. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res, 2014, 74(11): 2913-2921.
3. Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14(CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125): 1023-1075.
4. Xu Z, Shen J, Hua S, et al. High-throughput sequencing of circRNAs reveals novel insights into mechanisms of nigericin in pancreatic cancer. BMC Genomics, 2019, 20(1): 716.
5. Li J, Li Z, Jiang P, et al. Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis. J Exp Clin Cancer Res, 2018, 37(1): 177.
6. Li ZH, WU YF, Li J, et al. Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer. Cancer Lett, 2018, 432: 237-250.
7. Arnberg AC, Van Ommen GJ, Grivell LA, et al. Some yeast mitochondrial RNAs are circular. Cell, 1980, 19(2): 313-319.
8. 程龍, 王攀. circRNA的功能及其與胃癌關系的研究進展. 中國普外基礎與臨床雜志, 2019, 26(7): 892-896.
9. Zheng QP, Bao CY, Guo WJ, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun, 2016, 7: 11215.
10. 杜公博, 殷德濤. 環狀RNA在甲狀腺乳頭狀癌中的研究進展. 中國普外基礎與臨床雜志, 2020, 27(7): 890-894.
11. Haque S, Harries L W. Circular RNAs (circRNAs) in health and disease. Genes (Basel), 2017, 8(12): 353.
12. Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature, 2013, 495(7441): 384-388.
13. Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 2013, 495(7441): 333-338.
14. Liu L, Liu FB, Huang M, et al. Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway. Hepatobiliary Pancreat Dis Int, 2019, 18(6): 580-586.
15. Jiang PC, Bu SR. Clinical value of circular RNAs and autophagy-related miRNAs in the diagnosis and treatment of pancreatic cancer. Hepatobiliary Pancreat Dis Int, 2019, 18(6): 511-516.
16. Du WW, Yang W, Liu E, et al. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res, 2016, 44(6): 2846-2858.
17. Li Q, Wang Y, Wu S, et al. CircACC1 regulates assembly and activation of AMPK complex under metabolic stress. Cell Metab, 2019, 30(1): 157-173.
18. McGlynn L M, McCluney S, Jamieson N B, et al. SIRT3 & SIRT7: potential novel biomarkers for determining outcome in pancreatic cancer patients. PLoS One, 2015, 10(6): e0131344.
19. Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell, 2013, 51(6): 792-806.
20. Hansen TB, Wiklund ED, Bramsen JB, et al. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J, 2011, 30(21): 4414-4422.
21. Ng WL, Marinov GK, Liau ES, et al. Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway. RNA Biol, 2016, 13(9): 861-871.
22. Chen RX, Chen X, Xia LP, et al. N⁶-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun, 2019, 10(1): 4695.
23. Tatomer DC, Wilusz JE. An unchartered journey for ribosomes: circumnavigating circular RNAs to produce proteins. Mol Cell, 2017, 66(1): 1-2.
24. 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. Genome Biol, 2019, 20(1): 84.
25. Wang J, Zhu S, Meng N, et al. ncRNA-encoded peptides or proteins and cancer. Mol Ther, 2019, 27(10): 1718-1725.
26. Guo S, Xu X, Ouyang Y, et al. Microarray expression profile analysis of circular RNAs in pancreatic cancer. Mol Med Rep, 2018, 17(6): 7661-7671.
27. Yang F, Liu DY, Guo JT, et al. Circular RNA circ-LDLRAD3 as a biomarker in diagnosis of pancreatic cancer. World J Gastroenterol, 2017, 23(47): 8345-8354.
28. 王赫, 劉冬妍, 王晟, 等. 環狀RNA hsa-circ-0015022作為胰腺癌新型診斷生物標志物研究. 臨床軍醫雜志, 2020, 48(1): 30-34.
29. Whiteside TL. The effect of tumor-derived exosomes on immune regulation and cancer immunotherapy. Future Oncol, 2017, 13(28): 2583-2592.
30. Li Y, Zheng Q, Bao C, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res, 2015, 25(8): 981-984.
31. An Y, Cai H, Zhang Y, et al. circZMYM2 competed endogenously with miR-335-5p to regulate JMJD2C in pancreatic cancer. Cell Physiol Biochem, 2018, 51(5): 2224-2236.
32. Wong CH, Lou UK, Li Y, et al. CircFOXK2 promotes growth and metastasis of pancreatic ductal adenocarcinoma by complexing with RNA-binding proteins and sponging miR-942. Cancer Res, 2020, 80(11): 2138-2149.
33. Guo X, Zhou Q, Su D, et al. Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis. Mol Cancer, 2020, 19(1): 83.
34. Kong Y, Li Y, Luo Y, et al. circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer. Mol Cancer, 2020, 19(1): 82.
35. Gong R, Jiang Y. Non-coding RNAs in pancreatic ductal adenocarcinoma. Front Oncol, 2020, 10: 309.
36. Shi H, Li H, Zhen T, et al. hsa_circ_001653 Implicates in the development of pancreatic ductal adenocarcinoma by regulating microRNA-377-mediated HOXC6 axis. Mol Ther Nucleic Acids, 2020, 20: 252-264.
37. Yang J, Cong X, Ren M, et al. Circular RNA hsa_circRNA_0007334 is predicted to promote MMP7 and COL1A1 expression by functioning as a miRNA sponge in pancreatic ductal adenocarcinoma. J Oncol, 2019, 2019: 7630894.
38. Xing C, Ye H, Wang W, et al. Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression. Artif Cells Nanomed Biotechnol, 2019, 47(1): 3920-3928.
39. Liu Y, Xia L, Dong L, et al. CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by sponging miR-330-5p and targets RASSF1. Cancer Manag Res, 2020, 12: 921-929.
40. Huang WJ, Wang Y, Liu S, et al. Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression. Cancer Lett, 2018, 422: 70-80.
41. Xu C, Yu Y, Ding F. Microarray analysis of circular RNA expression profiles associated with gemcitabine resistance in pancreatic cancer cells. Oncol Rep, 2018, 40(1): 395-404.
42. Shao F, Huang M, Meng F, et al. Circular RNA signature predicts gemcitabine resistance of pancreatic ductal adenocarcinoma. Front Pharmacol, 2018, 9: 584.
43. Li H, Hao X, Wang H, et al. Circular RNA expression profile of pancreatic ductal adenocarcinoma revealed by microarray. Cell Physiol Biochem, 2016, 40(6): 1334-1344.
44. Takiuchi D, Eguchi H, Nagano H, et al. Involvement of microRNA-181b in the gemcitabine resistance of pancreatic cancer cells. Pancreatology, 2013, 13(5): 517-523.
45. Yang MC, Wang HC, Hou YC, et al. Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine. Mol Cancer, 2015, 14: 179.
46. Wei DM, Jiang MT, Lin P, et al. Potential ceRNA networks involved in autophagy suppression of pancreatic cancer caused by chloroquine diphosphate: A study based on differentially-expressed circRNAs, lncRNAs, miRNAs and mRNAs. Int J Oncol, 2019, 54(2): 600-626.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research status and prospect of circular RNA in pancreatic cancer

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