Long Non-coding RNA SNHG22 Facilitates Hepatocellular Carcinoma Tumorigenesis and Angiogenesis Via DNA Methylation of MicroRNA MiR-16-5p

Overview

Journal Bioengineered

Date 2021 Oct 15

PMID 34652260

Citations 15

Authors

Yinxin Zhang

Changliang Lu

Haiwei Cui

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is considered as a common malignancy worldwide. Considerable evidence has illustrated that abnormally expressed long noncoding RNAs (lncRNAs) are in a close correlation with the initiation and progression of various tumors, including HCC. LncRNA small nucleolar RNA host gene 22 (SNHG22) has been reported to play important roles in tumor initiation, but its role and mechanism are little known in HCC. In our report, we discovered the high level of SNHG22 in HCC tissues and cells, and the high expression of SNHG22 was correlated with unfavorable clinical outcome in HCC patients. Functional assays implied that SNHG22 deficiency suppressed cell proliferation, migration, invasion, and angiogenesis in vitro. Additionally, it was also confirmed that silenced SNHG22 suppressed tumor growth and angiogenesis in vivo. Mechanistic exploration revealed that SNHG22 recruited DNMT1 to miR-16-5p DNA promoter through EZH2 and inhibited miR-16-5p transcription via DNA methylation. Finally, we verified that the suppression of miR-16-5p countervailed the suppressive effect of SNHG22 deficiency on HCC cell proliferation, migration, invasion, and angiogenesis. Conclusively, this study clarified the SNHG22/EZH2/DNMT1/miR-16-5p axis and revealed that SNHG22 could be an underlying biomarker for HCC.

Citing Articles

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References

Kudo M, Kitano M, Sakurai T, Nishida N . Challenges of Clinical Research on Hepatocellular Carcinoma. Dig Dis. 2015; 33(6):780-90. DOI: 10.1159/000439103. View

Goh V, Sarker D, Osmany S, Cook G . Functional imaging techniques in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2012; 39(6):1070-9. DOI: 10.1007/s00259-012-2096-x. View

Gao H, Sun X, Wang H, Zheng Y . Long noncoding RNA SNHG22 increases ZEB1 expression via competitive binding with microRNA-429 to promote the malignant development of papillary thyroid cancer. Cell Cycle. 2020; 19(10):1186-1199. PMC: 7217354. DOI: 10.1080/15384101.2020.1749466. View

Djebali S, Davis C, Merkel A, Dobin A, Lassmann T, Mortazavi A . Landscape of transcription in human cells. Nature. 2012; 489(7414):101-8. PMC: 3684276. DOI: 10.1038/nature11233. View

Li W, Zheng J, Deng J, You Y, Wu H, Li N . Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells. Gastroenterology. 2014; 146(7):1714-26.e5. DOI: 10.1053/j.gastro.2014.03.002. View

Takagi K, Takada T, Amano H, Yoshida M, Miura H, Toyota N . Analysis of microvessels in pancreatic cancer: by light microscopy, confocal laser scan microscopy, and electron microscopy. J Hepatobiliary Pancreat Surg. 2008; 15(4):384-90. DOI: 10.1007/s00534-007-1241-6. View

Chang Z, Jia Y, Zhang W, Song L, Gao M, Li M . LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1. J Exp Clin Cancer Res. 2018; 37(1):56. PMC: 5848549. DOI: 10.1186/s13046-018-0724-4. View

Tian X, Wu Y, Yang Y, Wang J, Niu M, Gao S . Long noncoding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/β-catenin signaling. Mol Oncol. 2019; 14(2):462-483. PMC: 6998656. DOI: 10.1002/1878-0261.12606. View

Liu A, Zhang B, Zhao W, Tu Y, Wang Q, Li J . Catalpol ameliorates psoriasis-like phenotypes via SIRT1 mediated suppression of NF-κB and MAPKs signaling pathways. Bioengineered. 2020; 12(1):183-195. PMC: 8806253. DOI: 10.1080/21655979.2020.1863015. View

10.

Gou X, Zhao X, Wang Z . Long noncoding RNA PVT1 promotes hepatocellular carcinoma progression through regulating miR-214. Cancer Biomark. 2017; 20(4):511-519. DOI: 10.3233/CBM-170331. View

11.

Cai L, Ye L, Hu X, He W, Zhuang D, Guo Q . MicroRNA miR-330-3p suppresses the progression of ovarian cancer by targeting RIPK4. Bioengineered. 2021; 12(1):440-449. PMC: 8291835. DOI: 10.1080/21655979.2021.1871817. View

12.

Liu Y, Zhang H, Wang H, Du J, Dong P, Liu M . Long non-coding RNA DUXAP8 promotes the cell proliferation, migration, and invasion of papillary thyroid carcinoma via miR-223-3p mediated regulation of CXCR4. Bioengineered. 2021; 12(1):496-506. PMC: 8291844. DOI: 10.1080/21655979.2021.1882134. View

13.

Chava S, Reynolds C, Pathania A, Gorantla S, Poluektova L, Coulter D . miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma. Mol Oncol. 2019; 14(1):180-196. PMC: 6944109. DOI: 10.1002/1878-0261.12588. View

14.

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

15.

Wang C, Zhu C, Xu J, Wang M, Zhao W, Liu Q . The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer. 2019; 18(1):115. PMC: 6609402. DOI: 10.1186/s12943-019-1032-0. View

16.

Huang Y, Xu Y, Lu Y, Zhu S, Guo Y, Sun C . lncRNA Gm10451 regulates PTIP to facilitate iPSCs-derived β-like cell differentiation by targeting miR-338-3p as a ceRNA. Biomaterials. 2019; 216:119266. DOI: 10.1016/j.biomaterials.2019.119266. View

17.

Zhou Y, Huang Y, Dai T, Hua Z, Xu J, Lin Y . LncRNA TTN-AS1 intensifies sorafenib resistance in hepatocellular carcinoma by sponging miR-16-5p and upregulation of cyclin E1. Biomed Pharmacother. 2020; 133:111030. DOI: 10.1016/j.biopha.2020.111030. View

18.

Xu Y, Yao Y, Jiang X, Zhong X, Wang Z, Li C . SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma. J Exp Clin Cancer Res. 2018; 37(1):81. PMC: 5896100. DOI: 10.1186/s13046-018-0747-x. View

19.

Quinn J, Chang H . Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2015; 17(1):47-62. DOI: 10.1038/nrg.2015.10. View

20.

Zhou Y, Huan L, Wu Y, Bao C, Chen B, Wang L . LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8/ID2 pathway in hepatocellular carcinoma. Cancer Lett. 2019; 469:399-409. DOI: 10.1016/j.canlet.2019.11.007. View