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Circular RNA circ_0005835 promotes promoted neural stem cells proliferation and differentiate to neuron and inhibits inflammatory cytokines levels through miR-576-3p in Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease and it is difficult to have an effective and simple method for AD early diagnosis. CircRNAs (circular RNAs) are novel discovered non-coding endogenous RNAs that affect cell apoptosis, differentiation, growth, metabolism, and metastasis. Recently, it has reported that circ_0005835 was one upregulated circRNA in the AD patients. However, the function role of circ_0005835 remains unknown. In our study, we found that circ_0005835 was upregulated in AD patients and cell models. Knockdown of circ_0005835 could downregulate neuroinflammation in BV2 cells. Moreover, knockdown of circ_0005835 promoted neural stem cells (NSC) proliferation and differentiate to neuron. These data mean that circ_0005835 plays important role in the development of AD. The miR-576-3p expression in serum was downregulated in the AD group compared to the health control group. Consistently, the level of circ_0005835 was overexpressed in the Aβ-treated in both SH-SY5Y and BV2 cells. Moreover, the expression of miR-576-3p was negatively correlated with circ_0005835 in AD patients. In addition, we performed the rescued experiments to show that knockdown of circ_0005835 could downregulate neuroinflammation through sponging miR-576-3p in BV2 cells. Inhibition of circ_0005835 promoted NSC proliferation and differentiate to neuron via sponging miR-576-3p. These data suggested that circ_0005835 promoted AD development through regulating miR-576-3p expression.

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References

  • Akhter R (2018) Circular RNA and Alzheimer’s disease. Adv Exp Med Biol 1087:239–243

    Article  CAS  Google Scholar 

  • Banjara M, Ghosh C (2017) Sterile neuroinflammation and strategies for therapeutic intervention. Int J Inflamm 2017:8385961

    Article  Google Scholar 

  • Cao K, Xiang J, Dong YT, Xu Y, Li Y, Song H, Zeng XX, Ran LY, Hong W, Guan ZZ (2019) Exposure to fluoride aggravates the impairment in learning and memory and neuropathological lesions in mice carrying the APP/PS1 double-transgenic mutation. Alz Res Therapy 11:35

    Article  Google Scholar 

  • Cao L, Zhou X, Ding X, Gao D (2021) Knockdown of circPVT1 inhibits the progression of lung adenocarcinoma and enhances the sensitivity to cisplatin via the miR429/FOXK1 signaling axis. Mol Med Rep 24(4):684

  • Chen R, Wang Z, Zhi Z, Tian J, Zhao Y, Sun J (2021) Targeting the TLR4/NF-kappaB pathway in beta-amyloid-stimulated microglial cells: a possible mechanism that oxysophoridine exerts anti-oxidative and anti-inflammatory effects in an in vitro model of Alzheimer’s disease. Brain Res Bull 175:150–157

    Article  CAS  Google Scholar 

  • Cheng H, Wu B, Wang L, Hu T, Deng Z, Li D (2020) Insights into the expression profiles and functions of circRNAs in a newborn hyperoxia-induced rat bronchopulmonary dysplasia model. J Gene Med 22:e3163

    Article  CAS  Google Scholar 

  • Diling C, Yinrui G, Longkai Q, Xiaocui T, Yadi L, Xin Y, Guoyan H, Ou S, Tianqiao Y, Dongdong W, Yizhen X, Yang BB, Qingping W (2019) Circular RNA NF1-419 enhances autophagy to ameliorate senile dementia by binding Dynamin-1 and Adaptor protein 2 B1 in AD-like mice. Aging 11:12002–12031

    Article  Google Scholar 

  • Dong LX, Bao HL, Zhang YY, Liu Y, Zhang GW, An FM (2021): MicroRNA-16–5p/BTG2 axis affects neurological function, autophagy and apoptosis of hippocampal neurons in Alzheimer’s disease. Brain Res Bull 175:254–262

  • Ekstrom C, Puhto I, Kilander L (2021) Association between open-angle glaucoma and Alzheimer’s disease in Sweden: a long-term population-based follow-up study. Ups J Med Sci 21;126

  • Fracassi A, Marcatti M, Zolochevska O, Tabor N, Woltjer R, Moreno S, Taglialatela G (2021) Oxidative damage and antioxidant response in frontal cortex of demented and nondemented individuals with Alzheimer’s neuropathology. J Neurosci 41:538–554

  • Fu LY, Chen QQ, Yao T, Li TW, Ying S, Hu YR, Guo JM (2017) Hsa_circ_0005986 inhibits carcinogenesis by acting as a miR-129-5p sponge and is used as a novel biomarker for hepatocellular carcinoma. Oncotarget 8:43878–43888

    Article  Google Scholar 

  • Gong J, Xu X, Zhang X, Zhou Y (2020) Circular RNA-9119 suppresses in ovarian cancer cell viability via targeting the microRNA-21–5p-PTEN-Akt pathway. Aging 12(14):14314–14328

  • Huang X, He M, Huang S, Lin R, Zhan M, Yang D, Shen H, Xu S, Cheng W, Yu J, Qiu Z, Wang J (2019) Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription. Mol Cancer 18:166

    Article  CAS  Google Scholar 

  • Huaying C, Xing J, Luya J, Linhui N, Di S, Xianjun D (2020) A signature of five long non-coding RNAs for predicting the prognosis of Alzheimer’s disease based on competing endogenous RNA networks. Front Aging Neurosci 12:598606

    Article  Google Scholar 

  • JN V, M C, Y Z, S S, L X, YM W, SM D, CG E, X C, DR R, AI N, AM C (2019) The landscape of circular RNA in cancer. Cell 176: 869-881.e13

  • Lei B, Liu J, Yao Z, Xiao Y, Zhang X, Zhang Y, Xu J (2021) NF-kappaB-induced upregulation of miR-146a-5p promoted hippocampal neuronal oxidative stress and pyroptosis via TIGAR in a model of Alzheimer’s disease. Front Cell Neurosci 15:653881

    Article  CAS  Google Scholar 

  • Li F, Ma K, Sun M, Shi S (2018) Identification of the tumor-suppressive function of circular RNA ITCH in glioma cells through sponging miR-214 and promoting linear ITCH expression. Am J Transl Res 10:1373–1386

    CAS  Google Scholar 

  • Li Z, Chen Z, Feng Y, Hu G, Jiang Y (2020) CircMMP11 acts as a ce-circRNA in breast cancer progression by regulating miR-1204. Am J Transl Res 12:2585–2599

    CAS  Google Scholar 

  • Liang M, Huang G, Liu Z, Wang Q, Yu Z, Lin H, Li M, Zhou X, Zheng Y (2019) Elevated levels of hsa_circ_006100 in gastric cancer promote cell growth and metastasis via miR-195/GPRC5A signalling. Cell Prolif 52:e12661

    Article  Google Scholar 

  • Liu CG, Zhao Y, Lu Y, Wang PC (2021) ABCA1-labeled exosomes in serum contain higher microRNA-193b levels in Alzheimer’s disease. Biomed Res Int 2021:5450397

    Google Scholar 

  • Liu J, Song S, Lin S, Zhang M, Du Y, Zhang D, Xu W, Wang H (2019) Circ-SERPINE2 promotes the development of gastric carcinoma by sponging miR-375 and modulating YWHAZ. Cell Prolif 52:e12648

    Google Scholar 

  • Liu J, Zheng X, Liu H (2020a) Hsa_circ_0102272 serves as a prognostic biomarker and regulates proliferation, migration and apoptosis in thyroid cancer. J Gene Med e3209

  • Liu L, Chen X, Chen YH, Zhang K (2020b) Identification of circular RNA hsa_Circ_0003391 in peripheral blood is potentially associated with Alzheimer’s disease. Front Aging Neurosci 12:601965

    Article  CAS  Google Scholar 

  • LL C, (2016) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17:205–211

    Article  Google Scholar 

  • Lu Y, Tan L, Wang X (2019) Circular HDAC9/microRNA-138/Sirtuin-1 pathway mediates synaptic and amyloid precursor protein processing deficits in Alzheimer’s disease. Neurosci Bull 35:877–888

    Article  CAS  Google Scholar 

  • M L, G H, Z L, Q W, Z Y, H L, M L, X Z, Y Z (2019) Elevated levels of hsa_circ_006100 in gastric cancer promote cell growth and metastasis via miR-195/GPRC5A signalling. Cell Prolif 52: e12661

  • M Z, K Z, X X, Y Y, S Y, P W, H L, J X, F X, H Z, X Y, N H, J L, K H, K X, G Z, S H, N Z (2018): A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma. Nat Commun 9: 4475

  • Ma N, Pan J, Wen Y, Wu Q, Yu B, Chen X, Wan J, Zhang W (2021) circTulp4 functions in Alzheimer’s disease pathogenesis by regulating its parental gene, Tulp4. Mol Ther 29:2167–2181

    Article  CAS  Google Scholar 

  • Morton H, Kshirsagar S, Orlov E, Bunquin LE, Sawant N, Boleng L, George M, Basu T, Ramasubramanian B, Pradeepkiran JA, Kumar S, Vijayan M, Reddy AP, Reddy PH (2021) Defective mitophagy and synaptic degeneration in Alzheimer’s disease: focus on aging, mitochondria and synapse. Free Radical Biol Med 172:652–667

    Article  CAS  Google Scholar 

  • Ou GY, Lin WW, Zhao WJ (2021) Construction of long noncoding RNA-associated ceRNA networks reveals potential biomarkers in Alzheimer’s disease. JAD 82:169–183

    Article  CAS  Google Scholar 

  • Pan K, Chen S, Wang Y, Yao W, Gao X (2021) MicroRNA-23b attenuates tau pathology and inhibits oxidative stress by targeting GnT-III in Alzheimer’s disease. Neuropharmacology 196:108671

    Article  CAS  Google Scholar 

  • Pandey D, Pal T, Sharma A, Flora S (2021) Potential epigenetic targets for combating Alzheimer’s disease. Mini Rev Med Chem 21:1527–1540

    Article  CAS  Google Scholar 

  • Park M, Baik K, Lee YG, Kang SW, Jung JH, Jeong SH, Lee PH, Sohn YH, Ye BS (2021): Implication of small vessel disease MRI markers in Alzheimer’s disease and Lewy body disease. JAD 83(2):545–556

  • Q Z, G L, Z L, F G, J W, D Z, Y N (2018) CircRNA circ_0067934 promotes tumor growth and metastasis in hepatocellular carcinoma through regulation of miR-1324/FZD5/Wnt/β-catenin axis. Biochem Biophys Res Commun 497:626–632

  • Rasmussen ID, Boayue NM, Mittner M, Bystad M, Grnli OK, Vangberg TR, Csifcsak G, Aslaksen PM (2021) High-definition transcranial direct current stimulation improves delayed memory in Alzheimer’s disease patients: a pilot study using computational modeling to optimize electrode position. JAD 83(2):753–769

  • S H, X Z, B G, P S, CT H, J P, S T, J Y (2019): A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis. Am J Transl Res 11: 2455-2462

  • S M, M J, A E, F T, J K, A R, L M, SD M, LH G, M M, A L, U Z, M L, C K, F lN, N R (2013): Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495: 333-8

  • Tu F, Guo X, Wu H, He Z, Wang F, Sun A, Dai X (2020) Circ-0001313/miRNA-510-5p/AKT2 axis promotes the development and progression of colon cancer. Am J Transl Res 12:281–291

    CAS  Google Scholar 

  • Walgrave H et al. (2021) Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease. Cell stem cell 28(10):1805–1821.e8

  • X H, M H, S H, R L, M Z, D Y, H S, S X, W C, J Y, Z Q, J W (2019): Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription. Mol Cancer 18:166

  • Xu J, Lu W (2021) CircSPIDR acts as a tumour suppressor in cervical adenocarcinoma by sponging miR-431-5p and regulating SORCS1 and CUBN expression. Aging 13:18340–18359

    Article  CAS  Google Scholar 

  • Yang H, Wang H, Shang H, Chen X, Yang S, Qu Y, Ding J, Li X (2019) Circular RNA circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels via directly sponging miR-103 in Alzheimer’s disease. Cell Cycle 18:2197–2214

    Article  CAS  Google Scholar 

  • Yang KD, Wang Y, Zhang F, Luo BH, Feng DY, Zeng ZJ (2021) CircN4BP2L2 promotes colorectal cancer growth and metastasis through regulation of the miR-340–5p/CXCR4 axis. Lab Invest a journal of technical methods and pathology. Online ahead of print

  • Yin L, Chen J, Ma C, Pei S, Du M, Zhang Y, Feng Y, Yin R, Bian X, He X, Feng J (2020) Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3. Cell Death Dis 11:562

    Article  CAS  Google Scholar 

  • Z L, X C, D X, S L, MTV C, WKK W (2019): Circular RNAs in nucleus pulposus cell function and intervertebral disc degeneration. Cell Prolif 52: e12704

  • Zhang N, Gao Y, Yu S, Sun X, Shen K (2020a) Berberine attenuates Abeta42-induced neuronal damage through regulating circHDAC9/miR-142–5p axis in human neuronal cells. Life Sci 252:117637

    Article  CAS  Google Scholar 

  • Zhang P, Ren J, Wan J, Sun R, Li Y (2020b) Circular RNA hsa_circ_0002052 promotes osteosarcoma via modulating miR-382/STX6 axis. Hum Cell 33:810–818

    Article  CAS  Google Scholar 

  • Zhang T, Shen Y, Guo Y, Yao J (2021a) Identification of key transcriptome biomarkers based on a vital gene module associated with pathological changes in Alzheimer’s disease. Aging 13:14940–14967

    Article  CAS  Google Scholar 

  • Zhang W, Liu H, Jiang J, Yang Y, Wang W, Jia Z (2021b) CircRNA circFOXK2 facilitates oncogenesis in breast cancer via IGF2BP3/miR-370 axis. Aging 13:18978–18992

    Article  CAS  Google Scholar 

  • Zhang Z, Yang B, Zhou S, Wu J (2021c) CircRNA circ_SEC24A upregulates DNMT3A expression by sponging miR-26b-5p to aggravate osteoarthritis progression. Int Immunol 99:107957

    CAS  Google Scholar 

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Xiang Xu, Dean Gu, Bing Xu, Chenli Yang, and Ling Wang conducted experiments, collected and analyzed data, and write and revised this manuscript.

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Correspondence to Ling Wang.

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Communicated by Lotfi Aleya.

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Xu, X., Gu, D., Xu, B. et al. Circular RNA circ_0005835 promotes promoted neural stem cells proliferation and differentiate to neuron and inhibits inflammatory cytokines levels through miR-576-3p in Alzheimer’s disease. Environ Sci Pollut Res 29, 35934–35943 (2022). https://doi.org/10.1007/s11356-021-17478-3

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