Long non‑coding RNA NONHSAT143692.2 is involved in oxidative DNA damage repair in the lens by regulating the miR‑4728‑5p/OGG1 axis

Zhou,Tianqiu; Zhang,Junfang; Qin,Bai; Xu,Hui; Zhang,Shuqiang; Guan,Huaijin

doi:10.3892/ijmm.2020.4707

Long non‑coding RNA NONHSAT143692.2 is involved in oxidative DNA damage repair in the lens by regulating the miR‑4728‑5p/OGG1 axis

Authors:
- Tianqiu Zhou
- Junfang Zhang
- Bai Qin
- Hui Xu
- Shuqiang Zhang
- Huaijin Guan
View Affiliations

Affiliations: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Jiangsu Key Laboratory of Neurodegeneration, Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: August 24, 2020 https://doi.org/10.3892/ijmm.2020.4707
Pages: 1838-1848
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Age‑related cataract (ARC) is the leading cause of blindness worldwide. Oxidative DNA damage is a biochemical feature of ARC pathogenesis. The present study investigated the role of long non‑coding RNAs in the DNA repair of oxidative damage, partially the regulation of the DNA repair gene, 8‑oxoguanine DNA glycosylase (OGG1), in lens affected by ARC. The ogg1 mutant zebrafish model was constructed to verify the role of ogg1 in the lens. A high‑throughput lncRNA profiling was performed on human lens epithelial cells (LECs) following oxidative stress. The lncRNAs with the OGG1 target gene were analyzed for possible differentiated expression levels. The lens capsule samples of patients with ARC were collected to further verify the screening results. lncRNA was then overexpressed and knocked down in LECs to observe cell proliferation and apoptosis. The association between lncRNA, miRNA and the OGG1 mRNA 3'UTR were analyzed. The ogg1 mutant zebrafish developed more severe lens lesions following oxidative challenge. lncRNA NONHSAT143692.2 was distinctly expressed in various disease models. The knockdown of NONHSAT143692.2 downregulated the expression of OGG1 mRNA (P<0.001) and OGG1 protein (P<0.001), aggravated oxidative damage to LECs, increased apoptosis (P<0.001) and decreased cell proliferation (P<0.01). The overexpression of NONHSAT143692.2 reversed the above‑mentioned outcomes. miR‑4728‑5p was predicted to bind to NONHSAT143692.2 and OGG1 mRNA 3'UTR. The overexpression of miR‑4728‑5p downregulated the expression of NONHSAT143692.2 (P<0.001), OGG1 mRNA (P<0.001) and OGG1 protein (P<0.001). The knockdown of miR‑4728‑5p reversed the above‑mentioned outcomes. Overall, the findings of the present study demonstrate that the NONHSAT143692.2/miR‑4728‑5p/OGG1 axis may play an important role in the development of ARC. This novel concept may provide new insight into the molecular diagnosis and treatment of ARC.

View Figures

View References

1	Pascolini D and Mariotti SP: Global estimates of visual impairment: 2010. Br J Ophthalmol. 96:614–618. 2012. View Article : Google Scholar
2	Wei M, Xing KY, Fan YC, Libondi T and Lou MF: Loss of thiol repair systems in human cataractous lenses. Invest Ophthalmol Vis Sci. 56:598–605. 2014. View Article : Google Scholar : PubMed/NCBI
3	Khairallah M, Kahloun R, Bourne R, Limburg H, Flaxman SR, Jonas JB, Keeffe J, Leasher J, Naidoo K, Pesudovs K, et al: Number of people blind or visually impaired by cataract world-wide and in world regions, 1990 to 2010. Invest Ophthalmol Vis Sci. 56:6762–6769. 2015. View Article : Google Scholar : PubMed/NCBI
4	Chang JR, Koo E, Agrón E, Hallak J, Clemons T, Azar D, Sperduto RD, Ferris FL III, Chew EY, Age-Related Eye Disease and Study Group: Risk factors associated with incident cataracts and cataract surgery in the Age-related Eye Disease Study (AREDS): AREDS report number 32. Ophthalmology. 118:2113–2119. 2011. View Article : Google Scholar : PubMed/NCBI
5	Hejtmancik JF and Kantorow M: Molecular genetics of age-related cataract. Exp Eye Res. 79:3–9. 2004. View Article : Google Scholar : PubMed/NCBI
6	Zheng LR, Ma JJ, Zhou DX, An LF and Zhang YQ: Association between DNA repair genes (XPD and XRCC1) polymorphisms and susceptibility to age-related cataract (ARC): A meta-analysis. Graefes Arch Clin Exp Ophthalmol. 252:1259–1266. 2014. View Article : Google Scholar : PubMed/NCBI
7	Erol Tinaztepe Ö, Ay M and Eser E: Nuclear and mitochondrial DNA of age-related cataract patients are susceptible to oxidative damage. Curr Eye Res. 42:583–588. 2017. View Article : Google Scholar
8	Sorte K, Sune P, Bhake A, Shivkumar VB, Gangane N and Basak A: Quantitative assessment of DNA damage directly in lens epithelial cells from senile cataract patients. Mol Vis. 17:1–6. 2011.PubMed/NCBI
9	Cooke MS, Evans MD, Dizdaroglu M and Lunec J: Oxidative DNA damage: Mechanisms, mutation, and disease. FASEB J. 17:1195–1214. 2003. View Article : Google Scholar : PubMed/NCBI
10	Bruner SD, Norman DP and Verdine GL: Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature. 403:859–866. 2000. View Article : Google Scholar : PubMed/NCBI
11	Wu X, Lai W, Lin H and Liu Y: Association of OGG1 and MTHFR polymorphisms with age-related cataract: A systematic review and meta-analysis. PLoS One. 12:e01720922017. View Article : Google Scholar : PubMed/NCBI
12	Liu XC, Guo XH, Chen B, Li ZH and Liu XF: Association between the 8-oxoguanine DNA glycosylase gene Ser326Cys polymorphism and age-related cataract: A systematic review and meta-analysis. Int Ophthalmol. 38:1451–1457. 2018. View Article : Google Scholar
13	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
14	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
15	Quinn JJ and Chang HY: Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 17:47–62. 2016. View Article : Google Scholar
16	Shen Y, Dong LF, Zhou RM, Yao J, Song YC, Yang H, Jiang Q and Yan B: Role of long non-coding RNA MIAT in proliferation, apoptosis and migration of lens epithelial cells: A clinical and in vitro study. J Cell Mol Med. 20:537–548. 2016. View Article : Google Scholar : PubMed/NCBI
17	Li G, Song H, Chen L, Yang W, Nan K and Lu P: TUG1 promotes lens epithelial cell apoptosis by regulating miR-421/caspase-3 axis in age-related cataract. Exp Cell Res. 356:20–27. 2017. View Article : Google Scholar : PubMed/NCBI
18	Cheng T, Xu M, Qin B, Wu J, Tu Y, Kang L, Wang Y and Guan H: lncRNA H19 contributes to oxidative damage repair in the early age-related cataract by regulating miR-29a/TDG axis. J Cell Mol Med. 23:6131–6139. 2019. View Article : Google Scholar : PubMed/NCBI
19	Xiang J, Chen Q, Kang L, Zhang G, Wang Y, Qin B, Wu J, Zhou T, Han Y and Guan H: LncRNA PLCD3-OT1 functions as a CeRNA to prevent age-related cataract by sponging miR-224-5p and regulating PLCD3 expression. Invest Ophthalmol Vis Sci. 60:4670–4680. 2019. View Article : Google Scholar : PubMed/NCBI
20	Chylack LT Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA, Bailey IL, Friend J, McCarthy D and Wu SY: The lens opacities classification system III. The longitudinal study of cataract study group. Arch Ophthalmol. 111:831–836. 1993. View Article : Google Scholar : PubMed/NCBI
21	Jao LE, Wente SR and Chen W: Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc Natl Acad Sci USA. 110:13904–13909. 2013. View Article : Google Scholar : PubMed/NCBI
22	Prior HM, Letwin K, Tuininga A and Nguyen M: A simple method of cataract induction in adult zebrafish. Zebrafish. 15:211–212. 2018. View Article : Google Scholar : PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
24	Ji Y, Cai L, Zheng T, Ye H, Rong X, Rao J and Lu Y: The mechanism of UVB irradiation induced-apoptosis in cataract. Mol Cell Biochem. 401:87–95. 2015. View Article : Google Scholar
25	Jia Y, Qin Q, Fang CP, Shen W, Sun TT, Huang YL, Li WJ and Deng AM: UVB induces apoptosis via downregulation of CALML3-dependent JNK1/2 and ERK1/2 pathways in cataract. Int J Mol Med. 41:3041–3050. 2018.PubMed/NCBI
26	Carter RJ and Parsons JL: Base excision repair, a pathway regulated by posttranslational modifications. Mol Cell Biol. 36:1426–1437. 2016. View Article : Google Scholar : PubMed/NCBI
27	Wang AL, Lukas TJ, Yuan M and Neufeld AH: Increased mitochondrial DNA damage and downregulation of DNA repair enzymes in aged rodent retinal pigment epithelium and choroid. Mol Vis. 14:644–651. 2008.PubMed/NCBI
28	Synowiec E, Blasiak J, Zaras M, Szaflik J and Szaflik JP: Association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and age-related macular degeneration. Exp Eye Res. 98:58–66. 2012. View Article : Google Scholar : PubMed/NCBI
29	Peng Q, Lu Y, Lao X, Chen Z, Li R, Sui J, Qin X and Li S: Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: A meta-analysis. Diagn Pathol. 9:1082014. View Article : Google Scholar : PubMed/NCBI
30	Yousaf S, Khan AU, Akram Z, Kayani MA, Nadeem I, Begum B and Mahjabeen I: Expression deregulation of DNA repair pathway genes in gastric cancer. Cancer Genet. 237:39–50. 2019. View Article : Google Scholar : PubMed/NCBI
31	Wang Y, Li F, Zhang G, Kang L, Qin B and Guan H: Altered DNA methylation and expression profiles of 8-Oxoguanine DNA glycosylase 1 in lens tissue from age-related cataract patients. Curr Eye Res. 40:815–821. 2015. View Article : Google Scholar
32	Kang L, Zhao W, Zhang G, Wu J and Guan H: Acetylated 8-oxoguanine DNA Glycosylase 1 and its relationship with p300 and SIRT1 in lens epithelium cells from age-related cataract. Exp Eye Res. 135:102–108. 2015. View Article : Google Scholar : PubMed/NCBI
33	Congrains A, Kamide K, Ohishi M and Rakugi H: ANRIL: Molecular mechanisms and implications in human health. Int J Mol Sci. 14:1278–1292. 2013. View Article : Google Scholar : PubMed/NCBI
34	Liu JY, Yao J, Li XM, Song YC, Wang XQ, Li YJ, Yan B and Jiang Q: Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis. 5:e15062014. View Article : Google Scholar : PubMed/NCBI
35	Lu L, Yu X, Zhang L, Ding X, Pan H, Wen X, Xu S, Xing Y, Fan J, Ge S, et al: The long non-coding RNA RHPN1-AS1 promotes uveal melanoma progression. Int J Mol Sci. 18:2262017. View Article : Google Scholar :
36	Shang W, Yang Y, Zhang J and Wu Q: Long noncoding RNA BDNF-AS is a potential biomarker and regulates cancer development in human retinoblastoma. Biochem Biophys Res Commun. 497:1142–1148. 2018. View Article : Google Scholar
37	Liu Z, Zhang J, Gao J and Li Y: MicroRNA-4728 mediated regulation of MAPK oncogenic signaling in papillary thyroid carcinoma. Saudi J Biol Sci. 25:986–990. 2018. View Article : Google Scholar : PubMed/NCBI
38	Floros KV, Lochmann TL, Hu B, Monterrubio C, Hughes MT, Wells JD, Morales CB, Ghotra MS, Costa C, Souers AJ, et al: Coamplification of miR-4728 protects HER2-amplified breast cancers from targeted therapy. Proc Natl Acad Sci USA. 115:E2594–E2603. 2018. View Article : Google Scholar
39	Chiang CC, Lin CL, Peng CL, Sung FC and Tsai YY: Increased risk of cancer in patient with early-onset cataracts: A nationwide population-based study. Cancer Sci. 105:431–436. 2014. View Article : Google Scholar : PubMed/NCBI