Research status of antisense non-coding RNA in INK4 locus in long-chain non-coding RNA in diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Chen Shuze ¹ , Yu Zhengtong ¹ , Wang Zihong ¹ , Liang Xiaoqian ¹ , Zhong Huimin ¹ ,  Fu Min ²

1. The Second Medical College of Southern Medical University, Guangzhou 510515, China;
2. Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China;

Corresponding author：

Fu Min, Email: min_fu1212@163.com

Keywords：

Diabetic retinopathy; Review; Long-chain non-coding RNA; Antisense non-coding RNA in the ink4 locus

DOI：

10.3760/cma.j.issn.1005-1015.2020.01.019

Video：

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Abstract Full text Figures/Tables Video References Cited by

The pathogenesis of diabetic retinopathy (DR) is complex. Antisense non-coding RNA (ANRIL) in the INK4 locus in long-chain non-coding RNA (lncRNA) is closely related to cell proliferation, differentiation, and individual development. It plays an important role in the dysplasia of retinal vascular endothelial cells and is a new field in the study of the pathogenesis of DR. According to the researches at present, ANRIL may plays its role in the occurrence and development of DR through the signal pathway of nuclear factor-κB and ROS/polyadenylation diphosphate ribose polymerase, and interact with p300, miR-200b, and EZH2 to regulating the expression and function of VEGF. Specific blocking ANRIL and its related pathways may become a new target in the treatment of DR.

Citation： Chen Shuze, Yu Zhengtong, Wang Zihong, Liang Xiaoqian, Zhong Huimin, Fu Min. Research status of antisense non-coding RNA in INK4 locus in long-chain non-coding RNA in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2020, 36(1): 78-81. doi: 10.3760/cma.j.issn.1005-1015.2020.01.019 Copy

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2.	Thomas AA, Feng B, Chakrabarti S. ANRIL: a regulator of VEGF in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2017, 58(1): 470-480. DOI: 10.1167/iovs.16-20569.
3.	Kung JT, Colognori D, Lee JT. Long noncoding RNAs: past, present, and future[J]. Genetics, 2013, 193(3): 651-669. DOI: 10.1534/genetics.112.146704.
4.	Heo JB, Lee YS, Sung S. Epigenetic regulation by long noncoding RNAs in plants[J]. Chromosome Res, 2013, 21(6-7): 685-693. DOI: 10.1007/s10577-013-9392-6.
5.	Pasmant E, Laurendeau I, Héron D, et al. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF[J]. Cancer Res, 2007, 67(8): 3963-3969. DOI: 10.1158/0008-5472.CAN-06-2004.
6.	Cunnington MS, Santibanez KM, Mayosi BM, et al. Chromosome 9p21 SNPs Associated with multiple disease phenotypes correlate with ANRIL expression[J/OL]. PLoS Genet, 2010, 6(4): 1000899[2010-04-08]. https://doi.org/10.1371/journal.pgen.1000899. DOI:10.1371/journal.pgen.1000899.
7.	Holdt LM, Hoffmann S, Sass K, et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks[J/OL]. PLoS Genet, 2013, 9(7): 1003588[2013-07-04].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701717/. DOI:10.1371/journal.pgen.1003588.
8.	Burd CE, Jeck WR, Liu Y, et al. Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk[J/OL]. PLoS Genet, 2010, 6(12): 1001233[2010-12-02].https://doi.org/10.1371/journal.pgen.1001233. DOI:10.1371/journal.pgen.1001233.
9.	Zhang EB, Kong R, Yin DD, et al. Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a[J]. Oncotarget, 2014, 5(8): 2276-2292. DOI: 10.18632/oncotarget.1902.
10.	Pasmant E, Sabbagh A, Vidaud M, et al. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS[J]. FASEB J, 2011, 25(2): 444-448. DOI: 10.1096/fj.10-172452.
11.	Yu W, Gius D, Onyango P, et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA[J]. Nature, 2008, 451(7175): 202-206. DOI: 10.1038/nature06468.
12.	Aguilo F, Di Cecilia S, Walsh MJ. Long non-coding RNA ANRIL and polycomb in human cancers and cardiovascular disease[J]. Curr Top Microbiol Immunol, 2016, 394: 29-39. DOI: 10.1007/82-2015-455.
13.	Pasquale LR, Loomis SJ, Kang JH, et al. CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States[J]. Am J Ophthalmol, 2013, 155(2): 342-353. DOI: 10.1016/j.ajo.2012.07.023.
14.	Guil S, Soler M, Portela A, et al. Intronic RNAs mediate EZH2 regulation of epigenetic targets[J]. Nat Struct Mol Biol, 2012, 19(7): 664-670. DOI: 10.1038/nsmb.2315.
15.	Kong Y, Sharma RB, Nwosu BU, et al. Islet biology, the CDKN2A/B locus and type 2 diabetes risk[J]. Diabetologia, 2016, 59(8): 1579-1593. DOI: 10.1007/s00125-016-3967-7.
16.	Pullen TJ, Rutter GA. Could lncRNAs contribute to β-cell identity and its loss in type 2 diabetes?[J]. Biochem Soc Trans, 2013, 41(3): 797-801. DOI: 10.1042/BST20120355.
17.	Yan B, Tao ZF, Li XM, et al. Aberrant expression of long noncoding RNAs in early diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 941-951. DOI: 10.1167/iovs.13-13221.
18.	Debasish P, Toffa D, Gitanjali T. Pharmacognostic evaluation of curcumin on diabetic retinopathy in alloxan-induced diabetes through NF-κB and Brn3a related mechanism[J]. Phcog J, 2018, 10(2): 324-332. DOI: 10.5530/pj.2018.2.56.
19.	Choudhuri S, Chowdhury IH, Das S, et al. Role of NF-κB activation and VEGF gene polymorphisms in VEGF up regulation in non-proliferative and proliferative diabetic retinopathy[J]. Mol Cell Biochem, 2015, 405(1-2): 265-279. DOI: 10.1007/s11010-015-2417-z.
20.	Zhang B, Wang D, Ji TF, et al. Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-κB signaling pathway in a rat model[J/OL].Oncotarget, 2017, 8(10): 17347[2017-03-07]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370045/. DOI:10.18632/oncotarget.14468.
21.	Zhou X, Han X, Wittfeldt A, et al. Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway[J]. RNA Biol, 2015, 13(1): 98-108. DOI: 10.1080/15476286.2015.1122164.
22.	Wei JC, Shi YL, Wang Q. LncRNA ANRIL knockdown ameliorates retinopathy in diabetic rats by inhibiting the NF-kappaB pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(18): 7732-7739. DOI: 10.26355/eurrev-201909-18982.
23.	Mishra M, Kowluru RA. Role of PARP-1 as a novel transcriptional regulator of MMP-9 in diabetic retinopathy[J]. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(7): 1761-1769. DOI: 10.1016/j.bbadis.2017.04.024.
24.	Hammer SS, Beli E, Kady N, et al. The mechanism of diabetic retinopathy pathogenesis unifying key lipid regulators, sirtuin 1 and liver X receptor[J]. E Bio Medicine, 2017, 22: 181-190. DOI: 10.1016/j.ebiom.2017.07.008.
25.	Xu R, Mao Y, Chen K, et al. The long noncoding RNA ANRIL acts as an oncogene and contributes to paclitaxel resistance of lung adenocarcinoma A549 cells[J]. Oncotarget, 2017, 8(24): 39177-39184. DOI: 10.18632/oncotarget.16640.
26.	Zhu H, Li X, Song Y, et al. Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway[J]. Biochem Biophys Res Commun, 2015, 467(2): 223-228. DOI: 10.1016/j.bbrc.2015.10.002.
27.	Ruiz MA, Feng B, Chakrabarti S. Polycomb repressive complex 2 regulates MiR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy[J/OL].PLoS One 2015, 10(4): 123987[2015-04-17]. https://doi.org/10.1371/journal.pone.0123987. DOI:10.1371/journal.pone.0123987.
28.	Margueron R, Reinberg D. The polycomb complex PRC2 and its mark in life[J]. Nature, 2011, 469(7330): 343-349. DOI: 10.1038/nature09784.
29.	Yoo KH, Hennighausen L. EZH2 methyltransferase and H3K27 methylation in breast cancer[J]. Int J Biol Sci, 2012, 8(1): 59-65. DOI: 10.7150/ijbs.8.59.
30.	Chase A, Cross NC. Aberrations of EZH2 in cancer[J]. Clin Cancer Res, 2011, 17(9): 2613-2618. DOI: 10.1158/1078-0432.CCR-10-2156.
31.	Yap KL, Li S, Munoz-Cabello AM, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a[J]. Mol Cell, 2010, 38(5): 662-674. DOI: 10.1016/j.molcel.2010.03.021.
32.	Thomas AA, Feng B, Chakrabarti S. ANRIL regulates production of extracellular matrix proteins and vasoactive factors in diabetic complications[J]. Am J Physiol Endocrinol Metab, 2018, 314(3): 191-200. DOI: 10.1152/ajpendo.00268.2017.
33.	Yang ZZ, Zhang Y, Chen X, et al. Total synthesis and evaluation of new B-homo palmatine and berberine derivatives as p300 histone acetyltransferase inhibitors[J]. Eur J Org Chem, 2018, 2018(8): 1041-1052. DOI: 10.1002/ejoc.201701693.
34.	Meseure D, Vacher S, Alsibai KD, et al. Expression of ANRIL-Polycomb complexes- CDKN2A/B/ARF genes in breast tumors: identification of a two-gene (EZH2/CBX7) signature with independent prognostic value[J]. Mol Cancer Res, 2016, 14(7): 623-633. DOI: 10.1158/1541-7786.MCR-15-0418.
35.	Korpal M, Lee ES, Hu G, et al. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2[J]. J Biol Chem, 2008, 283(22): 14910-14914. DOI: 10.1074/jbc.C800074200.
36.	Xi Y, Chang H. MIR200B (microRNA 200b)[J]. Altas Genet Cytogenet Oncol Haematol, 2016, 20(5): 273-274. DOI: 10.4267/2042/62776.
37.	Peng F, Jiang J, Yu Y, et al. Direct targeting of SUZ12/ROCK2 by miR-200b/c inhibits cholangiocarcinoma tumourigenesis and metastasis[J]. Br J Cancer, 2013, 109(12): 3092-3104. DOI: 10.1038/bjc.2013.655.
38.	Mcarthur K, Feng B, Wu Y, et al. MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy[J]. Diabetes, 2011, 60(4): 1314-1323. DOI: 10.2337/db10-1557.
39.	Li EH, Huang QZ, Li GC, et al. Effects of miRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene[J/OL]. Biosci Rep, 2017, 37(2): 20160572[2017-04-30]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484021/. DOI:10.1042/BSR20160572.

1. Yarmishyn AA, Kurochkin IV. Long noncoding RNAs: a potential novel class of cancer biomarkers[J/OL]. Front Genet, 2015, 6: 145[2015-04-23]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407501/. DOI:10.3389/fgene.2015.00145.
2. Thomas AA, Feng B, Chakrabarti S. ANRIL: a regulator of VEGF in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2017, 58(1): 470-480. DOI: 10.1167/iovs.16-20569.
3. Kung JT, Colognori D, Lee JT. Long noncoding RNAs: past, present, and future[J]. Genetics, 2013, 193(3): 651-669. DOI: 10.1534/genetics.112.146704.
4. Heo JB, Lee YS, Sung S. Epigenetic regulation by long noncoding RNAs in plants[J]. Chromosome Res, 2013, 21(6-7): 685-693. DOI: 10.1007/s10577-013-9392-6.
5. Pasmant E, Laurendeau I, Héron D, et al. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF[J]. Cancer Res, 2007, 67(8): 3963-3969. DOI: 10.1158/0008-5472.CAN-06-2004.
6. Cunnington MS, Santibanez KM, Mayosi BM, et al. Chromosome 9p21 SNPs Associated with multiple disease phenotypes correlate with ANRIL expression[J/OL]. PLoS Genet, 2010, 6(4): 1000899[2010-04-08]. https://doi.org/10.1371/journal.pgen.1000899. DOI:10.1371/journal.pgen.1000899.
7. Holdt LM, Hoffmann S, Sass K, et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks[J/OL]. PLoS Genet, 2013, 9(7): 1003588[2013-07-04].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701717/. DOI:10.1371/journal.pgen.1003588.
8. Burd CE, Jeck WR, Liu Y, et al. Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk[J/OL]. PLoS Genet, 2010, 6(12): 1001233[2010-12-02].https://doi.org/10.1371/journal.pgen.1001233. DOI:10.1371/journal.pgen.1001233.
9. Zhang EB, Kong R, Yin DD, et al. Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a[J]. Oncotarget, 2014, 5(8): 2276-2292. DOI: 10.18632/oncotarget.1902.
10. Pasmant E, Sabbagh A, Vidaud M, et al. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS[J]. FASEB J, 2011, 25(2): 444-448. DOI: 10.1096/fj.10-172452.
11. Yu W, Gius D, Onyango P, et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA[J]. Nature, 2008, 451(7175): 202-206. DOI: 10.1038/nature06468.
12. Aguilo F, Di Cecilia S, Walsh MJ. Long non-coding RNA ANRIL and polycomb in human cancers and cardiovascular disease[J]. Curr Top Microbiol Immunol, 2016, 394: 29-39. DOI: 10.1007/82-2015-455.
13. Pasquale LR, Loomis SJ, Kang JH, et al. CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States[J]. Am J Ophthalmol, 2013, 155(2): 342-353. DOI: 10.1016/j.ajo.2012.07.023.
14. Guil S, Soler M, Portela A, et al. Intronic RNAs mediate EZH2 regulation of epigenetic targets[J]. Nat Struct Mol Biol, 2012, 19(7): 664-670. DOI: 10.1038/nsmb.2315.
15. Kong Y, Sharma RB, Nwosu BU, et al. Islet biology, the CDKN2A/B locus and type 2 diabetes risk[J]. Diabetologia, 2016, 59(8): 1579-1593. DOI: 10.1007/s00125-016-3967-7.
16. Pullen TJ, Rutter GA. Could lncRNAs contribute to β-cell identity and its loss in type 2 diabetes?[J]. Biochem Soc Trans, 2013, 41(3): 797-801. DOI: 10.1042/BST20120355.
17. Yan B, Tao ZF, Li XM, et al. Aberrant expression of long noncoding RNAs in early diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 941-951. DOI: 10.1167/iovs.13-13221.
18. Debasish P, Toffa D, Gitanjali T. Pharmacognostic evaluation of curcumin on diabetic retinopathy in alloxan-induced diabetes through NF-κB and Brn3a related mechanism[J]. Phcog J, 2018, 10(2): 324-332. DOI: 10.5530/pj.2018.2.56.
19. Choudhuri S, Chowdhury IH, Das S, et al. Role of NF-κB activation and VEGF gene polymorphisms in VEGF up regulation in non-proliferative and proliferative diabetic retinopathy[J]. Mol Cell Biochem, 2015, 405(1-2): 265-279. DOI: 10.1007/s11010-015-2417-z.
20. Zhang B, Wang D, Ji TF, et al. Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-κB signaling pathway in a rat model[J/OL].Oncotarget, 2017, 8(10): 17347[2017-03-07]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370045/. DOI:10.18632/oncotarget.14468.
21. Zhou X, Han X, Wittfeldt A, et al. Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway[J]. RNA Biol, 2015, 13(1): 98-108. DOI: 10.1080/15476286.2015.1122164.
22. Wei JC, Shi YL, Wang Q. LncRNA ANRIL knockdown ameliorates retinopathy in diabetic rats by inhibiting the NF-kappaB pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(18): 7732-7739. DOI: 10.26355/eurrev-201909-18982.
23. Mishra M, Kowluru RA. Role of PARP-1 as a novel transcriptional regulator of MMP-9 in diabetic retinopathy[J]. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(7): 1761-1769. DOI: 10.1016/j.bbadis.2017.04.024.
24. Hammer SS, Beli E, Kady N, et al. The mechanism of diabetic retinopathy pathogenesis unifying key lipid regulators, sirtuin 1 and liver X receptor[J]. E Bio Medicine, 2017, 22: 181-190. DOI: 10.1016/j.ebiom.2017.07.008.
25. Xu R, Mao Y, Chen K, et al. The long noncoding RNA ANRIL acts as an oncogene and contributes to paclitaxel resistance of lung adenocarcinoma A549 cells[J]. Oncotarget, 2017, 8(24): 39177-39184. DOI: 10.18632/oncotarget.16640.
26. Zhu H, Li X, Song Y, et al. Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway[J]. Biochem Biophys Res Commun, 2015, 467(2): 223-228. DOI: 10.1016/j.bbrc.2015.10.002.
27. Ruiz MA, Feng B, Chakrabarti S. Polycomb repressive complex 2 regulates MiR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy[J/OL].PLoS One 2015, 10(4): 123987[2015-04-17]. https://doi.org/10.1371/journal.pone.0123987. DOI:10.1371/journal.pone.0123987.
28. Margueron R, Reinberg D. The polycomb complex PRC2 and its mark in life[J]. Nature, 2011, 469(7330): 343-349. DOI: 10.1038/nature09784.
29. Yoo KH, Hennighausen L. EZH2 methyltransferase and H3K27 methylation in breast cancer[J]. Int J Biol Sci, 2012, 8(1): 59-65. DOI: 10.7150/ijbs.8.59.
30. Chase A, Cross NC. Aberrations of EZH2 in cancer[J]. Clin Cancer Res, 2011, 17(9): 2613-2618. DOI: 10.1158/1078-0432.CCR-10-2156.
31. Yap KL, Li S, Munoz-Cabello AM, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a[J]. Mol Cell, 2010, 38(5): 662-674. DOI: 10.1016/j.molcel.2010.03.021.
32. Thomas AA, Feng B, Chakrabarti S. ANRIL regulates production of extracellular matrix proteins and vasoactive factors in diabetic complications[J]. Am J Physiol Endocrinol Metab, 2018, 314(3): 191-200. DOI: 10.1152/ajpendo.00268.2017.
33. Yang ZZ, Zhang Y, Chen X, et al. Total synthesis and evaluation of new B-homo palmatine and berberine derivatives as p300 histone acetyltransferase inhibitors[J]. Eur J Org Chem, 2018, 2018(8): 1041-1052. DOI: 10.1002/ejoc.201701693.
34. Meseure D, Vacher S, Alsibai KD, et al. Expression of ANRIL-Polycomb complexes- CDKN2A/B/ARF genes in breast tumors: identification of a two-gene (EZH2/CBX7) signature with independent prognostic value[J]. Mol Cancer Res, 2016, 14(7): 623-633. DOI: 10.1158/1541-7786.MCR-15-0418.
35. Korpal M, Lee ES, Hu G, et al. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2[J]. J Biol Chem, 2008, 283(22): 14910-14914. DOI: 10.1074/jbc.C800074200.
36. Xi Y, Chang H. MIR200B (microRNA 200b)[J]. Altas Genet Cytogenet Oncol Haematol, 2016, 20(5): 273-274. DOI: 10.4267/2042/62776.
37. Peng F, Jiang J, Yu Y, et al. Direct targeting of SUZ12/ROCK2 by miR-200b/c inhibits cholangiocarcinoma tumourigenesis and metastasis[J]. Br J Cancer, 2013, 109(12): 3092-3104. DOI: 10.1038/bjc.2013.655.
38. Mcarthur K, Feng B, Wu Y, et al. MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy[J]. Diabetes, 2011, 60(4): 1314-1323. DOI: 10.2337/db10-1557.
39. Li EH, Huang QZ, Li GC, et al. Effects of miRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene[J/OL]. Biosci Rep, 2017, 37(2): 20160572[2017-04-30]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484021/. DOI:10.1042/BSR20160572.

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Research status of antisense non-coding RNA in INK4 locus in long-chain non-coding RNA in diabetic retinopathy

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