Expression and clinical significance of peripheral blood lncRNA MALAT1 and miR-199b in patients with proliferative diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

 Li Caihong ¹ , Chen Yanchen ²

1. Department of Ophthalmology, The First People's Hospital of Shuangliu District of Chengdu (West China Airport Hospital of Sichuan University), Chengdu 610200, China;
2. Sichuan Eye Hospital, Chengdu 610200, China;

Corresponding?author：

Li Caihong, Email: zqing1988@yeah.net

Keywords：

Proliferative diabetic retinopathy; LncRNA in peripheral blood; Metastasis-associated lung adenocarcinoma transcript 1; miR-199b; Peripheral blood; Aqueous humor; Prediction; Biomarker

DOI：

10.3760/cma.j.cn511434-20250819-00361

Video：

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Objective To investigate the expression and clinical significance of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-199b in the peripheral blood of patients with proliferative diabetic retinopathy (PDR). Methods A retrospective clinical study. A total of 473 patients with type 2 diabetes (T2DM) who visited Department of Ophthalmology of West China Airport Hospital of Sichuan University from February 2022 to July 2024 were included in the study. According to the diagnostic criteria for diabetic retinopathy (DR) in the Chinese Clinical Diagnosis and Treatment Guidelines for Diabetic Retinopathy, the T2DM patients were divided into three groups: the non-DR group (NDR group, 130 cases), the non-PDR group (NPDR group, 132 cases), and the PDR group (211 cases). Another 120 patients of the same age and gender who underwent simple cataract surgery during the same period were selected as the cataract group. Blood pressure, and laboratory data including fasting blood glucose (FBG), fasting insulin (FINS), glycated hemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were collected in detail for the T2DM group patients. Fasting peripheral venous blood was collected from T2DM group patients; aqueous humor was collected from 45 PDR and NPDR patients with concurrent macular edema before intravitreal injection of anti-vascular endothelial growth factor drugs. The expression levels of lncRNA MALAT1 and miR-199b mRNA in peripheral blood and aqueous humor were detected by quantitative real-time polymerase chain reaction. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the efficacy of lncRNA MALAT1 and miR-199b alone and in combination for predicting PDR occurrence. One-way analysis of variance was used for comparisons among multiple groups. The correlation between the expression levels of the two indicators and each clinical parameter was analyzed using Pearson correlation analysis. Results Compared with the NPDR group and the NDR group, the systolic blood pressure, FBG, HbA1c, FINS and TG levels of patients in the PDR group were significantly increased, while HDL-C levels were significantly decreased. The differences were statistically significant (F=42.207, 52.320, 478.335, 107.676, 86.273, 77.653; P＜0.05); the expression of peripheral blood lncRNA MALAT1 was significantly increased, while the expression of miR-199b was significantly decreased, and the differences were statistically significant (F=31.773, 152.784; P＜0.05). Compared with the NPDR group and the cataract group, the expression of lncRNA MALAT1 in the aqueous humor of patients in the PDR group was significantly increased, and the expression of miR-199b was significantly decreased (F=159.700, 114.667; P＜0.05). The correlation analysis results showed that the expression of peripheral blood lncRNA MALAT1 was positively correlated with systolic blood pressure, FBG, HbA1c, TG, and FINS (r=0.318, 0.358, 0.689, 0.474, 0.498), and negatively correlated with miR-199b (r=?0.526) and HDL-C (r=?0.489) (P＜0.05). The expression of miR-199b showed an opposite correlation with the above metabolic indicators (r=?0.419, ?0.425, ?0.712, ?0.516, ?0.541, 0.529; P＜0.05). The expression levels of lncRNA MALAT1 and miR-199b in the peripheral blood and aqueous humor of PDR patients were significantly positively correlated (r=0.732, 0.675; P＜0.05). ROC curve analysis showed that the AUC values of peripheral blood lncRNA MALAT1, miR-199b alone and in combination for predicting PDR were 0.684, 0.796, and 0.861, respectively. Conclusions Patients with PDR exhibit high expression of lncRNA MALAT1 and low expression of miR-199b in peripheral blood. The expressions of these markers are consistent between peripheral blood and aqueous humor and are associated with glucose and lipid metabolism. Their combination demonstrates high predictive value for the occurrence of PDR.

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2.	范雯, 王曉玲, 馬梟, 等. 基于超廣角熒光素眼底血管造影圖像行糖尿病視網膜病變分期的多模態深度學習模型研究[J]. 中華眼底病雜志, 2022, 38(2): 139-145. DOI: 10.3760/cma.j.cn511434-20211231-00736.Fan W, Wang XL, Ma X, et al. Multimodal deep learning model for staging diabetic retinopathy based on ultra-widefield fluorescence angiographyJ]. Chin J Ocul Fundus Dis, 2022, 38(2): 139-145. DOI: 10.3760/cma.j.cn511434-20211231-00736.
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4.	Hu Z, Wang J, Pan T, et al. The Exosome-transmitted incRNA LOC100132249 induces endothelial dysfunction in diabetic retinopathy[J]. Diabetes, 2023, 72(9): 1307-1319. DOI: 10.2337/db22-0435.
5.	Mohammad G, Kumar J, Kowluru RA. Mitochondrial genome-encoded long noncoding RNA cytochrome B and mitochondrial dysfunction in diabetic retinopathy[J]. Antioxid Redox Signal, 2023, 39(13-15): 817-828. DOI: 10.1089/ars.2023.0303.
6.	陳前波, 席曉婷, 馬嘉, 等. lncRNA MALAT1通過miR-124-3p/SOX7分子軸促進視網膜血管內皮細胞增殖及遷移和血管生成[J]. 國際眼科雜志, 2022, 22(10): 1608-1614. DOI: 10.3980/j.issn.1672-5123.2022.10.02.Chen QB, Xi XT, Ma J, et al. Research on the IncRNA MALAT1 promoting the proliferation, migration and angiogenesis of retinal vascular endothelial cells in diabetic retinopathy through the molecular axis of miR-124-3p/SOX7[J]. Int Eye Sci, 2022, 22(10): 1608-1614. DOI: 10.3980/j.issn.1672-5123.2022.10.02.
7.	Chen Z, Yang J, Gao Y, et al. LncRNA MALAT1 aggravates the retinal angiogenesis via miR-320a/HIF-1α axis in diabetic retinopathy[J/OL]. Exp Eye Res, 2022, 218: 108984[2022-05-01]. https://pubmed.ncbi.nlm.nih.gov/35202706/. DOI: 10.1016/j.exer.2022.108984.
8.	毛旖旎, 胡雁, 侯勝平, 等. 大鼠角膜緣新生血管微小RNA與血管內皮生長因子相關性分析[J]. 重慶醫科大學學報, 2014, 39(8): 1090-1094. DOI: 10.13406/j.cnki.cyxb.000324.Mao YN, Hu Y, Hou SP, et al. Correlation between microRNA expression profiles and VEGF of corneal neovascularization in rats[J]. J Chongqing Med Univ, 2014, 39(8): 1090-1094. DOI: 10.13406/j.cnki.cyxb.000324.
9.	梅雪迎. 香菇菌絲體多糖通過調控LncRNA MALAT1/miR-199b/mTOR軸抑制AGEs誘導HUVEC細胞焦亡的作用研究[D]. 沈陽: 遼寧大學, 2023.Mei XY. Study on the effect of Lentinula edodes mycelia polysaccharides in inhibiting AGEs-induced HUVEC pyroptosis by regulating the LncRNA MALAT1/miR-199b/mTOR axis[D]. Shenyang: Liaoning University, 2023.
10.	中華醫學會糖尿病學分會. 中國2型糖尿病防治指南(2017年版)[J]. 中華糖尿病雜志, 2018, 10(1): 4-67. DOI: 10.3760/cma.j.issn.1674-5809.2018.01.003.Chinese Diabetes Society of the Chinese Medical Association. Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2017 Edition)[J]. Chin J Diabetes Mellitus, 2018, 10(1): 4-67. DOI: 10.3760/cma.j.issn.1674-5809.2018.01.003.
11.	中華醫學會眼科學分會眼底病學組,中國醫師協會眼科醫師分會眼底病學組. 我國糖尿病視網膜病變臨床診療指南(2022年)—基于循證醫學修訂[J]. 中華眼底病雜志, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.Fundus Disease Group of Ophthalmological Society of Chinese Medical Association, Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association. Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China (2022)[J]. Chin J Ocul Fundus Dis, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.
12.	Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus[J/OL]. Cell Death Dis, 2014, 5(10): e1506[2014-10-30]. https://pubmed.ncbi.nlm.nih.gov/25356875/. DOI: 10.1038/cddis.2014.466.
13.	Zhao W, Liu Y, Li C, et al. Mechanisms of MALAT1 regulating proliferative diabetic retinopathy via targeting miR-126-5p[J]. Am J Transl Res, 2023, 15(5): 3279-3289.
14.	Tian Y, Cheng W, Wang H, et al. Ascorbic acid protects retinal pigment epithelial cells from high glucose by inhibiting the NF-κB signal pathway through MALAT1/IGF2BP3 axis[J/OL]. Diabet Med, 2023, 40(5): e15050[2023-02-07]. https://pubmed.ncbi.nlm.nih.gov/36661363/. DOI: 10.1111/dme.15050.
15.	Ebrahimi R, Toolabi K, Jannat Ali Pour N, et al. Adipose tissue gene expression of long non-coding RNAs; MALAT1, TUG1 in obesity: is it associated with metabolic profile and lipid homeostasis-related genes expression?[J/OL]. Diabetol Metab Syndr, 2020, 12: 36[2020-04-29]. https://pubmed.ncbi.nlm.nih.gov/32368256/. DOI: 10.1186/s13098-020-00544-0.
16.	Luo F, Liu X, Ling M, et al. The lncRNA MALAT1, acting through HIF-1α stabilization, enhances arsenite-induced glycolysis in human hepatic L-02 cells[J]. Biochim Biophys Acta, 2016, 1862(9): 1685-1695. DOI: 10.1016/j.bbadis.2016.06.004.
17.	王瑋, 王偉, 李婷婷. 晚期結直腸癌患者血清微小RNA-199b和微小RNA-203水平檢測及其預后預測價值分析[J]. 陜西醫學雜志, 2024, 53(6): 832-837. DOI: 10.3969/j.issn.1000-7377.2024.06.024.Wang W, Wang W, Li TT. Detection and prognostic value of serum microRNA-199b and microRNA-203 levels in patients with advanced colorectal cancer[J]. Shaanxi Med J, 2024, 53(6): 832-837. DOI: 10.3969/j.issn.1000-7377.2024.06.024.
18.	Hong SA, Lee S, Park J, et al. miR-199a and miR-199b facilitate diffuse gastric cancer progression by targeting Frizzled-6[J/OL]. Sci Rep, 2023, 13(1): 17480[2023-10-14]. https://pubmed.ncbi.nlm.nih.gov/37838767/. DOI: 10.1038/s41598-023-44716-0.
19.	Reithmair M, Buschmann D, M?rte M, et al. Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis[J]. J Cell Mol Med, 2017, 21(10): 2403-2411. DOI: 10.1111/jcmm.13162.
20.	Lin X, Qiu W, Xiao Y, et al. MiR-199b-5p suppresses tumor angiogenesis mediated by vascular endothelial cells in breast cancer by targeting ALK1[J/OL]. Front Genet, 2020, 10: 1397[20220-01-30]. https://pubmed.ncbi.nlm.nih.gov/32082362/. DOI: 10.3389/fgene.2019.01397.

1. Lin KY, Hsih WH, Lin YB, et al. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy[J]. J Diabetes Investig, 2021, 12(8): 1322-1325. DOI: 10.1111/jdi.13480.
2. 范雯, 王曉玲, 馬梟, 等. 基于超廣角熒光素眼底血管造影圖像行糖尿病視網膜病變分期的多模態深度學習模型研究[J]. 中華眼底病雜志, 2022, 38(2): 139-145. DOI: 10.3760/cma.j.cn511434-20211231-00736.Fan W, Wang XL, Ma X, et al. Multimodal deep learning model for staging diabetic retinopathy based on ultra-widefield fluorescence angiographyJ]. Chin J Ocul Fundus Dis, 2022, 38(2): 139-145. DOI: 10.3760/cma.j.cn511434-20211231-00736.
3. Lin W, Feng M, Liu T, et al. Microvascular changes after conbercept intravitreal injection of PDR with or without center-involved diabetic macular edema analyzed by OCTA[J/OL]. Front Med (Lausanne), 2022, 9: 797087[2022-03-22]. https://pubmed.ncbi.nlm.nih.gov/35391880/. DOI: 10.3389/fmed.2022.797087.
4. Hu Z, Wang J, Pan T, et al. The Exosome-transmitted incRNA LOC100132249 induces endothelial dysfunction in diabetic retinopathy[J]. Diabetes, 2023, 72(9): 1307-1319. DOI: 10.2337/db22-0435.
5. Mohammad G, Kumar J, Kowluru RA. Mitochondrial genome-encoded long noncoding RNA cytochrome B and mitochondrial dysfunction in diabetic retinopathy[J]. Antioxid Redox Signal, 2023, 39(13-15): 817-828. DOI: 10.1089/ars.2023.0303.
6. 陳前波, 席曉婷, 馬嘉, 等. lncRNA MALAT1通過miR-124-3p/SOX7分子軸促進視網膜血管內皮細胞增殖及遷移和血管生成[J]. 國際眼科雜志, 2022, 22(10): 1608-1614. DOI: 10.3980/j.issn.1672-5123.2022.10.02.Chen QB, Xi XT, Ma J, et al. Research on the IncRNA MALAT1 promoting the proliferation, migration and angiogenesis of retinal vascular endothelial cells in diabetic retinopathy through the molecular axis of miR-124-3p/SOX7[J]. Int Eye Sci, 2022, 22(10): 1608-1614. DOI: 10.3980/j.issn.1672-5123.2022.10.02.
7. Chen Z, Yang J, Gao Y, et al. LncRNA MALAT1 aggravates the retinal angiogenesis via miR-320a/HIF-1α axis in diabetic retinopathy[J/OL]. Exp Eye Res, 2022, 218: 108984[2022-05-01]. https://pubmed.ncbi.nlm.nih.gov/35202706/. DOI: 10.1016/j.exer.2022.108984.
8. 毛旖旎, 胡雁, 侯勝平, 等. 大鼠角膜緣新生血管微小RNA與血管內皮生長因子相關性分析[J]. 重慶醫科大學學報, 2014, 39(8): 1090-1094. DOI: 10.13406/j.cnki.cyxb.000324.Mao YN, Hu Y, Hou SP, et al. Correlation between microRNA expression profiles and VEGF of corneal neovascularization in rats[J]. J Chongqing Med Univ, 2014, 39(8): 1090-1094. DOI: 10.13406/j.cnki.cyxb.000324.
9. 梅雪迎. 香菇菌絲體多糖通過調控LncRNA MALAT1/miR-199b/mTOR軸抑制AGEs誘導HUVEC細胞焦亡的作用研究[D]. 沈陽: 遼寧大學, 2023.Mei XY. Study on the effect of Lentinula edodes mycelia polysaccharides in inhibiting AGEs-induced HUVEC pyroptosis by regulating the LncRNA MALAT1/miR-199b/mTOR axis[D]. Shenyang: Liaoning University, 2023.
10. 中華醫學會糖尿病學分會. 中國2型糖尿病防治指南(2017年版)[J]. 中華糖尿病雜志, 2018, 10(1): 4-67. DOI: 10.3760/cma.j.issn.1674-5809.2018.01.003.Chinese Diabetes Society of the Chinese Medical Association. Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2017 Edition)[J]. Chin J Diabetes Mellitus, 2018, 10(1): 4-67. DOI: 10.3760/cma.j.issn.1674-5809.2018.01.003.
11. 中華醫學會眼科學分會眼底病學組,中國醫師協會眼科醫師分會眼底病學組. 我國糖尿病視網膜病變臨床診療指南(2022年)—基于循證醫學修訂[J]. 中華眼底病雜志, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.Fundus Disease Group of Ophthalmological Society of Chinese Medical Association, Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association. Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China (2022)[J]. Chin J Ocul Fundus Dis, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.
12. Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus[J/OL]. Cell Death Dis, 2014, 5(10): e1506[2014-10-30]. https://pubmed.ncbi.nlm.nih.gov/25356875/. DOI: 10.1038/cddis.2014.466.
13. Zhao W, Liu Y, Li C, et al. Mechanisms of MALAT1 regulating proliferative diabetic retinopathy via targeting miR-126-5p[J]. Am J Transl Res, 2023, 15(5): 3279-3289.
14. Tian Y, Cheng W, Wang H, et al. Ascorbic acid protects retinal pigment epithelial cells from high glucose by inhibiting the NF-κB signal pathway through MALAT1/IGF2BP3 axis[J/OL]. Diabet Med, 2023, 40(5): e15050[2023-02-07]. https://pubmed.ncbi.nlm.nih.gov/36661363/. DOI: 10.1111/dme.15050.
15. Ebrahimi R, Toolabi K, Jannat Ali Pour N, et al. Adipose tissue gene expression of long non-coding RNAs; MALAT1, TUG1 in obesity: is it associated with metabolic profile and lipid homeostasis-related genes expression?[J/OL]. Diabetol Metab Syndr, 2020, 12: 36[2020-04-29]. https://pubmed.ncbi.nlm.nih.gov/32368256/. DOI: 10.1186/s13098-020-00544-0.
16. Luo F, Liu X, Ling M, et al. The lncRNA MALAT1, acting through HIF-1α stabilization, enhances arsenite-induced glycolysis in human hepatic L-02 cells[J]. Biochim Biophys Acta, 2016, 1862(9): 1685-1695. DOI: 10.1016/j.bbadis.2016.06.004.
17. 王瑋, 王偉, 李婷婷. 晚期結直腸癌患者血清微小RNA-199b和微小RNA-203水平檢測及其預后預測價值分析[J]. 陜西醫學雜志, 2024, 53(6): 832-837. DOI: 10.3969/j.issn.1000-7377.2024.06.024.Wang W, Wang W, Li TT. Detection and prognostic value of serum microRNA-199b and microRNA-203 levels in patients with advanced colorectal cancer[J]. Shaanxi Med J, 2024, 53(6): 832-837. DOI: 10.3969/j.issn.1000-7377.2024.06.024.
18. Hong SA, Lee S, Park J, et al. miR-199a and miR-199b facilitate diffuse gastric cancer progression by targeting Frizzled-6[J/OL]. Sci Rep, 2023, 13(1): 17480[2023-10-14]. https://pubmed.ncbi.nlm.nih.gov/37838767/. DOI: 10.1038/s41598-023-44716-0.
19. Reithmair M, Buschmann D, M?rte M, et al. Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis[J]. J Cell Mol Med, 2017, 21(10): 2403-2411. DOI: 10.1111/jcmm.13162.
20. Lin X, Qiu W, Xiao Y, et al. MiR-199b-5p suppresses tumor angiogenesis mediated by vascular endothelial cells in breast cancer by targeting ALK1[J/OL]. Front Genet, 2020, 10: 1397[20220-01-30]. https://pubmed.ncbi.nlm.nih.gov/32082362/. DOI: 10.3389/fgene.2019.01397.

Chinese Journal of Ocular Fundus Diseases

Latest ArticlesExpression and clinical significance of peripheral blood lncRNA MALAT1 and miR-199b in patients with proliferative diabetic retinopathy

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