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Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis

  • Authors:
    • Qiajun Du
    • Jie Han
    • Shan Gao
    • Shangdi Zhang
    • Yunyan Pan
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China, Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
    Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 388
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    Published online on: October 29, 2020
       https://doi.org/10.3892/ol.2020.12251
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Abstract

Hypoxia facilitates the progression of numerous cancers. Circular RNAs (circRNA) have been revealed to be involved in the process of tumors mediated by hypoxia. However, the role and molecular mechanism of circular RNA hsa_circ_0008450 (circ_0008450) in hepatocellular cancer (HCC) under hypoxic conditions has been rarely reported. Expression levels of circ_0008450, microRNA(miR)‑431 and A‑kinase anchor protein 1 (AKAP1) were examined using reverse transcription‑quantitative PCR. Cell viability, apoptosis and glycolysis were assessed via Cell Counting Kit‑8, flow cytometry and glycolysis assays, respectively. The association between circ_0008450 or AKAP1 and miR‑431 was verified via dual‑luciferase reporter assays. Protein levels of AKAP1 were detected by western blotting. Effect of hsa_circ_0008450 on tumor growth in vivo was confirmed by xenograft assays. Circ_0008450 was upregulated in HCC tissues and hypoxia‑disposed HCC cells. Depletion of circ_0008450 suppressed tumor growth in vivo and reversed the repression of apoptosis and the acceleration of viability and glycolysis of HCC cells induced by hypoxia treatment in vitro. Notably, circ_0008450 regulated AKAP1 expression by sponging miR‑431. Furthermore, miR‑431 inhibition reversed the circ_0008450 silencing‑mediated effects on viability, apoptosis and glycolysis in hypoxia‑treated HCC cells. Additionally, AKAP1 enhancement abolished the effects of miR‑431 upregulation on the viability, apoptosis and glycolysis in hypoxia‑treated HCC cells. In conclusion, circ_0008450 repression mitigated the progression of HCC under hypoxia by downregulating AKAP1 via miR‑431, providing a potential target for HCC treatment.
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View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Forner A, Llovet JM and Bruix J: Hepatocellular carcinoma. Lancet. 379:1245–1255. 2012. View Article : Google Scholar : PubMed/NCBI

3 

El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Zhu P, Ning Y, Yao L, Chen M and Xu C: The proliferation, apoptosis, invasion of endothelial-like epithelial ovarian cancer cells induced by hypoxia. J Exp Clin Cancer Res. 29:1242010. View Article : Google Scholar : PubMed/NCBI

5 

Du C, Weng X, Hu W, Lv Z, Xiao H, Ding C, Gyabaah OA, Xie H, Zhou L, Wu J, et al: Hypoxia-inducible MiR-182 promotes angiogenesis by targeting RASA1 in hepatocellular carcinoma. J Exp Clin Cancer Res. 34:672015. View Article : Google Scholar : PubMed/NCBI

6 

Rankin EB and Giaccia AJ: Hypoxic control of metastasis. Science. 352:175–180. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Su Y, Yang W, Jiang N, Shi J, Chen L, Zhong G, Bi J, Dong W, Wang Q, Wang C, et al: Hypoxia-elevated circELP3 contributes to bladder cancer progression and cisplatin resistance. Int J Biol Sci. 15:441–452. 2019. View Article : Google Scholar : PubMed/NCBI

8 

Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N and Kadener S: circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 56:55–66. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Ebbesen KK, Hansen TB and Kjems J: Insights into circular RNA biology. RNA Biol. 14:1035–1045. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Zhao ZJ and Shen J: Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol. 14:514–521. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Wang R, Zhang S, Chen X, Li N, Li J, Jia R, Pan Y and Liang H: CircNT5E acts as a sponge of miR-422a to promote glioblastoma tumorigenesis. Cancer Res. 78:4812–4825. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Qiu M, Xia W, Chen R, Wang S, Xu Y, Ma Z, Xu W, Zhang E, Wang J, Fang T, et al: The circular RNA circPRKCI promotes tumor growth in lung adenocarcinoma. Cancer Res. 78:2839–2851. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Ren S, Liu J, Feng Y, Li Z, He L, Li L, Cao X, Wang Z and Zhang Y: Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia. J Exp Clin Cancer Res. 38:3882019. View Article : Google Scholar : PubMed/NCBI

14 

Wei Y, Zhang Y, Meng Q, Cui L and Xu C: Hypoxia-induced circular RNA has_circRNA_403658 promotes bladder cancer cell growth through activation of LDHA. Am J Transl Res. 11:6838–6849. 2019.PubMed/NCBI

15 

Su H, Zou D, Sun Y and Dai Y: Hypoxia-associated circDENND2A promotes glioma aggressiveness by sponging miR-625-5p. Cell Mol Biol Lett. 24:242019. View Article : Google Scholar : PubMed/NCBI

16 

Wei H, Liu D, Sun J, Mao Y, Zhao L, Zhu W, Xu G and Gao Z: Circular RNA circ_0008450 upregulates CXCL9 expression by targeting miR-577 to regulate cell proliferation and invasion in nasopharyngeal carcinoma. Exp Mol Pathol. 110:1042882019. View Article : Google Scholar : PubMed/NCBI

17 

Zhang J, Chang Y, Xu L and Qin L: Elevated expression of circular RNA circ_0008450 predicts dismal prognosis in hepatocellular carcinoma and regulates cell proliferation, apoptosis, and invasion via sponging miR-548p. J Cell Biochem. 120:9487–9494. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Lu TX and Rothenberg ME: MicroRNA. J Allergy Clin Immunol. 141:1202–1207. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Krol J, Loedige I and Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 11:597–610. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Yang J, Zhu H, Jin Y and Song Y: MiR-431 inhibits cell proliferation and induces cell apoptosis by targeting CDK14 in pancreatic cancer. Eur Rev Med Pharmacol Sci. 22:4493–4499. 2018.PubMed/NCBI

21 

Su WB and Liu ZY: MiR-431 inhibits colorectal cancer cell invasion via repressing CUL4B. Eur Rev Med Pharmacol Sci. 22:3047–3052. 2018.PubMed/NCBI

22 

Xu CM, Chen LX, Gao F, Zhu MF, Dai Y, Xu Y and Qian WX: MiR-431 suppresses proliferation and metastasis of lung cancer via down-regulating DDX5. Eur Rev Med Pharmacol Sci. 23:699–707. 2019.PubMed/NCBI

23 

Sun K, Zeng T, Huang D, Liu Z, Huang S, Liu J and Qu Z: MicroRNA-431 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the ZEB1-mediated epithelial-mensenchymal transition. FEBS Open Bio. 5:900–907. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Feliciello A, Gottesman ME and Avvedimento EV: The biological functions of A-kinase anchor proteins. J Mol Biol. 308:99–114. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Rinaldi L, Sepe M, Delle Donne R, Conte K, Arcella A, Borzacchiello D, Amente S, De Vita F, Porpora M, Garbi C, et al: Mitochondrial AKAP1 supports mTOR pathway and tumor growth. Cell Death Dis. 8:e28422017. View Article : Google Scholar : PubMed/NCBI

26 

Schiattarella GG, Cattaneo F, Carrizzo A, Paolillo R, Boccella N, Ambrosio M, Damato A, Pironti G, Franzone A, Russo G, et al: Akap1 regulates vascular function and endothelial cells behavior. Hypertension. 71:507–517. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Yu J, Zhang Y, Zhou D, Wu J and Luo R: Higher expression of A-kinase anchoring-protein 1 predicts poor prognosis in human hepatocellular carcinoma. Oncol Lett. 16:131–136. 2018.PubMed/NCBI

28 

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

29 

Jiang ZJ, Shen QH, Chen HY, Yang Z, Shuai MQ and Zheng SS: Galectin-1 gene silencing inhibits the activation and proliferation but induces the apoptosis of hepatic stellate cells from mice with liver fibrosis. Int J Mol Med. 43:103–116. 2019.PubMed/NCBI

30 

Rankin EB, Nam JM and Giaccia AJ: Hypoxia: Signaling the metastatic cascade. Trends Cancer. 2:295–304. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Zhang X, Li Y, Ma Y, Yang L, Wang T, Meng X, Zong Z, Sun X, Hua X and Li H: Yes-associated protein (YAP) binds to HIF-1α and sustains HIF-1α protein stability to promote hepatocellular carcinoma cell glycolysis under hypoxic stress. J Exp Clin Cancer Res. 37:2162018. View Article : Google Scholar : PubMed/NCBI

32 

Ou ZL and Luo Z: Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells: Role of circ_0000977/miR-153 axis. RNA Biol. 16:1592–1603. 2019. View Article : Google Scholar : PubMed/NCBI

33 

Lin T, Dai Y, Guo X, Chen W, Zhao J, Cao L and Wu Z: Silencing of hsa_circ_0008450 represses hepatocellular carcinoma progression through regulation of microRNA-214-3p/EZH2 axis. Cancer Manag Res. 11:9133–9143. 2019. View Article : Google Scholar : PubMed/NCBI

34 

Liu Y, Li L, Liu Z, Yuan Q and Lu X: Downregulation of MiR-431 expression associated with lymph node metastasis and promotes cell invasion in papillary thyroid carcinoma. Cancer Biomark. 22:727–732. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Li MF, Li YH, He YH, Wang Q, Zhang Y, Li XF, Meng XM, Huang C and Li J: Emerging roles of hsa_circ_0005075 targeting miR-431 in the progress of HCC. Biomed Pharmacother. 99:848–858. 2018. View Article : Google Scholar : PubMed/NCBI

36 

Carlucci A, Adornetto A, Scorziello A, Viggiano D, Foca M, Cuomo O, Annunziato L, Gottesman M and Feliciello A: Proteolysis of AKAP121 regulates mitochondrial activity during cellular hypoxia and brain ischaemia. EMBO J. 27:1073–1084. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Du Q, Han J, Gao S, Zhang S and Pan Y: Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis. Oncol Lett 20: 388, 2020.
APA
Du, Q., Han, J., Gao, S., Zhang, S., & Pan, Y. (2020). Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis. Oncology Letters, 20, 388. https://doi.org/10.3892/ol.2020.12251
MLA
Du, Q., Han, J., Gao, S., Zhang, S., Pan, Y."Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis". Oncology Letters 20.6 (2020): 388.
Chicago
Du, Q., Han, J., Gao, S., Zhang, S., Pan, Y."Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis". Oncology Letters 20, no. 6 (2020): 388. https://doi.org/10.3892/ol.2020.12251
Copy and paste a formatted citation
x
Spandidos Publications style
Du Q, Han J, Gao S, Zhang S and Pan Y: Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis. Oncol Lett 20: 388, 2020.
APA
Du, Q., Han, J., Gao, S., Zhang, S., & Pan, Y. (2020). Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis. Oncology Letters, 20, 388. https://doi.org/10.3892/ol.2020.12251
MLA
Du, Q., Han, J., Gao, S., Zhang, S., Pan, Y."Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis". Oncology Letters 20.6 (2020): 388.
Chicago
Du, Q., Han, J., Gao, S., Zhang, S., Pan, Y."Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis". Oncology Letters 20, no. 6 (2020): 388. https://doi.org/10.3892/ol.2020.12251
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