LncRNA HOTAIR improves diabetic cardiomyopathy by increasing viability of cardiomyocytes through activation of the PI3K/Akt pathway

Qi,Kun; Zhong,Jianke

doi:10.3892/etm.2018.6755

LncRNA HOTAIR improves diabetic cardiomyopathy by increasing viability of cardiomyocytes through activation of the PI3K/Akt pathway

Authors:
- Kun Qi
- Jianke Zhong
View Affiliations

Affiliations: Department of Gerontology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Published online on: September 18, 2018 https://doi.org/10.3892/etm.2018.6755
Pages: 4817-4823

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

The current study aimed to investigate the role of long non‑coding RNA (lncRNA) homeobox transcript antisense RNA (HOTAIR) in the pathogenesis of diabetic cardiomyopathy. Patients with diabetic cardiomyopathy, patients with diabetes but without cardiomyopathy and healthy controls were included in the current study. All participants underwent myocardial biopsy to collect myocardial tissues. Blood samples were also collected from each participant to prepare serum. Expression of HOTAIR in myocardial tissues was detected by reverse transcription‑quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of serum HOTAIR for diabetic cardiomyopathy. AC16 human cardiomyocyte cells were treated with high glucose to observe the changes in expression of HOTAIR and phosphorylation of Akt. HOTAIR expression vector was transfected into cells of AC16 cell line and the effects of HOTAIR overexpression on cell viability and Akt phosphorylation were detected by MTT assay and western blot analysis, respectively. HOTAIR expression was significantly downregulated in myocardial tissues and serum of patients with diabetic cardiomyopathy compared with patients with diabetes and healthy controls. Serum HOTAIR could be used to effectively distinguish patients with diabetic cardiomyopathy from healthy controls. High glucose treatment inhibited HOTAIR expression and Akt phosphorylation. HOTAIR overexpression promoted Akt phosphorylation. HOTAIR overexpression improved AC16 cell viability, while PI3K/Akt inhibitor treatment reduced this effect. LncRNA HOTAIR may improve diabetic cardiomyopathy by increasing the viability of cardiomyocytes through activation of the PI3K/Akt pathway.

View Figures

View References

1	Alberti KG and Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation. Diabetic Med. 15:539–553. 1998. View Article : Google Scholar : PubMed/NCBI
2	Imamura F, O'Connor L, Ye Z, Mursu J, Hayashino Y, Bhupathiraju SN and Forouhi NG: Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: Systematic review, meta-analysis, and estimation of population attributable fraction. BMJ. 351:h35762015. View Article : Google Scholar : PubMed/NCBI
3	Nathan DM: DCCT/EDIC Research Group: The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: Overview. Diabetes Care. 37:9–16. 2014. View Article : Google Scholar : PubMed/NCBI
4	Bugger H and Abel ED: Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 57:660–671. 2014. View Article : Google Scholar : PubMed/NCBI
5	Huynh K, Bernardo BC, McMullen JR and Ritchie RH: Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther. 142:375–415. 2014. View Article : Google Scholar : PubMed/NCBI
6	Jia G, DeMarco VG and Sowers JR: Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat Rev Endocrinol. 12:144–153. 2016. View Article : Google Scholar : PubMed/NCBI
7	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Gen. 15:7–21. 2014. View Article : Google Scholar
8	Nunes S, Rolo AP, Palmeira CM and Reis F: Diabetic cardiomyopathy: Focus on oxidative stress, mitochondrial dysfunction and inflammation. Cardiomyopathies-Types and Treatments. InTech. 2017. View Article : Google Scholar
9	Li X, Wang H, Yao B, Xu W, Chen J and Zhou X: lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy. Sci Rep. 6:363402016. View Article : Google Scholar : PubMed/NCBI
10	Wang K, Long B, Zhou LY, Liu F, Zhou QY, Liu CY, Fan YY and Li PF: CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun. 5:35962014. View Article : Google Scholar : PubMed/NCBI
11	Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010. View Article : Google Scholar : PubMed/NCBI
12	Wu H, Liu J, Li W, Liu G and Li Z: LncRNA-HOTAIR promotes TNF-α production in cardiomyocytes of LPS-induced sepsis mice by activating NF-κB pathway. Biochem Biophys Res Commun. 471:240–246. 2016. View Article : Google Scholar : PubMed/NCBI
13	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 : PubMed/NCBI
14	Leung A, Amaram V and Natarajan R: Linking diabetic vascular complications with LncRNAs. Vasc Pharmacol. 2018. View Article : Google Scholar
15	Zhou X, Zhang W, Jin M, Chen J, Xu W and Kong X: lncRNA MIAT functions as a competing endogenous RNA to upregulate DAPK2 by sponging miR-22-3p in diabetic cardiomyopathy. Cell death Dis. 8:29292017. View Article : Google Scholar
16	Zhang M, Gu H, Xu W and Zhou X: Down-regulation of lncRNA MALAT1 reduces cardiomyocyte apoptosis and improves left ventricular function in diabetic rats. Int J cardiol. 203:214–216. 2016. View Article : Google Scholar : PubMed/NCBI
17	Marcinkiewicz A, Ostrowski S and Drzewoski J: Can the onset of heart failure be delayed by treating diabetic cardiomyopathy? Diabetol Metab Syndr. 9:212017. View Article : Google Scholar : PubMed/NCBI
18	Grammatikakis I, Panda AC, Abdelmohsen K and Gorospe M: Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging. Aging (Albany NY). 6:9922014. View Article : Google Scholar : PubMed/NCBI
19	Mayfield RD: Emerging roles for ncRNAs in alcohol use disorders. Alcohol. 60:31–39. 2017. View Article : Google Scholar : PubMed/NCBI
20	Wang J, Qiu M, Xu Y, Li M, Dong G, Mao Q, Yin R and Xu L: Long noncoding RNA CCAT2 correlates with smoking in esophageal squamous cell carcinoma. Tumor Biol. 36:5523–5528. 2015. View Article : Google Scholar
21	Chen S, Liu J, Liu X, Fu Y, Zhang M, Lin Q, Zhu J, Mai L, Shan Z, Yu X, et al: Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes. J Ethnopharmacol. 137:263–270. 2011. View Article : Google Scholar : PubMed/NCBI
22	Cai L and Kang YJ: Cell death and diabetic cardiomyopathy. Cardiovasc Toxicol. 3:219–228. 2003. View Article : Google Scholar : PubMed/NCBI
23	Yan J, Dang Y, Liu S, Zhang Y and Zhang G: LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes. Tumor Biol. 2016. View Article : Google Scholar
24	Qiu JJ, Wang Y, Ding JX, Jin HY, Yang G and Hua KQ: The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis. Exp Cell Res. 333:238–248. 2015. View Article : Google Scholar : PubMed/NCBI
25	Chen J, Lin C, Yong W, Ye Y and Huang Z: Calycosin and genistein induce apoptosis by inactivation of HOTAIR/p-Akt signaling pathway in human breast cancer MCF-7 cells. Cell Physiol Biochem. 35:722–728. 2015. View Article : Google Scholar : PubMed/NCBI