OpenLB
Open Library of Bioscience
Advanced Search
Biochemical genetics
Oct, 2021;59 (5): 1311-1325.

lncRNA SNHG16 Mediates Cell Proliferation and Apoptosis in Cholangiocarcinoma by Directly Targeting miR-146a-5p/GATA6 Axis.

Tao Wu, Ming-Sheng Lei, Xu-Zhao Gao, Ting-Gang Xiong, Kang Yang, Qian Gong, Rui Tang, Yue-Peng Tian, Xiao-Hua Fu
Author Information
  1. Tao Wu: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China. happyfei2006@163.com. ORCID
  2. Ming-Sheng Lei: Department of Respiratory Medicine, Zhangjiajie People's Hospital, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
  3. Xu-Zhao Gao: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
  4. Ting-Gang Xiong: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
  5. Kang Yang: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
  6. Qian Gong: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
  7. Rui Tang: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
  8. Yue-Peng Tian: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
  9. Xiao-Hua Fu: Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
PMID: 33797690 DOI: 10.1007/s10528-021-10059-6

Abstract

Cholangiocarcinoma (CCA) is a malignant tumour with high recurrence and mortality rates and poor prognosis. However, the pathogenic mechanism remains unclear. In the present study, we aimed to investigate the roles and regulatory mechanism of SNHG16 in the occurrence and development of CCA. Gene Expression Profiling Interactive Analysis (GEPIA) was used to predict the expressions of SNHG16 and GATA6 in CCA samples from TCGA database. The levels of SNHG16, miR-146a-5p and GATA6 were evaluated using qRT-PCR. CCK-8 and flow cytometry assays were conducted to evaluate cell proliferation and apoptosis, respectively. Western blotting was applied to analyse the protein levels of GATA6 and apoptosis-related proteins. SNHG16 was significantly elevated in CCA tissues from TCGA database and CCA cell lines. Moreover, downregulation of SNHG16 restricted cell proliferation and increased apoptotic rate of RBE and HuCCT1 cells. miR-146a-5p, a downstream target of SNHG16, was shown to be an intermediate mediator of GATA6 expression regulated by SNHG16. In addition, either the miR-146a-5p inhibitor or overexpression of GATA6 obviously impaired the regulatory effects of SNHG16 downregulation in RBE and HuCCT1 cells. These data demonstrated that SNHG16 promoted cell proliferation and repressed apoptosis by regulating the miR-146a-5p/GATA6 axis, which provides some helpful insights for the diagnosis and treatment of CCA.

Keywords

Apoptosis Cholangiocarcinoma GATA6 LncRNA SNHG16 Proliferation

References

Adams BD, Parsons C, Walker L, Zhang WC, Slack FJ (2017) Targeting noncoding RNAs in disease. J Clin Invest 127:761–771. https://doi.org/10.1172/JCI84424 [DOI: 10.1172/JCI84424]
Adelman K, Egan E (2017) Non-coding RNA: more uses for genomic junk. Nature 543:183–185. https://doi.org/10.1038/543183a [DOI: 10.1038/543183a]
Blechacz B (2017) Cholangiocarcinoma: current knowledge and new developments. Gut Liver 11:13–26. https://doi.org/10.5009/gnl15568 [DOI: 10.5009/gnl15568]
Cai C, Huo Q, Wang X, Chen B, Yang Q (2017) SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. Biochem Biophys Res Commun 485:272–278. https://doi.org/10.1016/j.bbrc.2017.02.094 [DOI: 10.1016/j.bbrc.2017.02.094]
Cao X, Xu J, Yue D (2018) LncRNA-SNHG16 predicts poor prognosis and promotes tumor proliferation through epigenetically silencing p21 in bladder cancer. Cancer Gene Ther 25:10–17. https://doi.org/10.1038/s41417-017-0006-x [DOI: 10.1038/s41417-017-0006-x]
Christensen LL et al (2016) SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism. Mol Oncol 10:1266–1282. https://doi.org/10.1016/j.molonc.2016.06.003 [DOI: 10.1016/j.molonc.2016.06.003]
Deniz E, Erman B (2017) Long noncoding RNA (lincRNA), a new paradigm in gene expression control. Funct Integr Genom 17:135–143. https://doi.org/10.1007/s10142-016-0524-x [DOI: 10.1007/s10142-016-0524-x]
Fan X, Shi Z, Sun X (2014) Association of single nucleotide polymorphism of rs2910164 in pre-miR-146a sequence with cholangiocarcinoma. Chin J Gen Surg 23(8):1067–1071
Huang L et al (2019) Long non-coding RNA NNT-AS1 functions as an oncogenic gene through modulating miR-485/BCL9 in cholangiocarcinoma. Cancer Manag Res 11:7739–7749. https://doi.org/10.2147/CMAR.S207801 [DOI: 10.2147/CMAR.S207801]
Iacona JR, Lutz CS (2019) miR-146a-5p: expression, regulation, and functions in cancer. Wiley Interdiscip Rev RNA 10:e1533. https://doi.org/10.1002/wrna.1533 [DOI: 10.1002/wrna.1533]
Iacona JR, Monteleone NJ, Lemenze AD, Cornett AL, Lutz CS (2019) Transcriptomic studies provide insights into the tumor suppressive role of miR-146a-5p in non-small cell lung cancer (NSCLC) cells. RNA Biol 16:1721–1732. https://doi.org/10.1080/15476286.2019.1657351 [DOI: 10.1080/15476286.2019.1657351]
Kapranov P et al (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488. https://doi.org/10.1126/science.1138341 [DOI: 10.1126/science.1138341]
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853–858. https://doi.org/10.1126/science.1064921 [DOI: 10.1126/science.1064921]
Lamarca A, Hubner RA, David Ryder W, Valle JW (2014) Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol 25:2328–2338. https://doi.org/10.1093/annonc/mdu162 [DOI: 10.1093/annonc/mdu162]
Li YL et al (2016) MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell lines by targeting CCND1 and CCND2. Oncotarget 7:59287–59298. https://doi.org/10.18632/oncotarget.11040 [DOI: 10.18632/oncotarget.11040]
Li X, Jin Y, Mu Z, Chen W, Jiang S (2017) MicroRNA-146a-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes. Int J Oncol 51:327–335. https://doi.org/10.3892/ijo.2017.4023 [DOI: 10.3892/ijo.2017.4023]
Liu S, Zhang W, Liu K, Liu Y (2019) LncRNA SNHG16 promotes tumor growth of pancreatic cancer by targeting miR-218-5p. Biomed Pharmacother = Biomedecine & pharmacotherapie 114:108862. https://doi.org/10.1016/j.biopha.2019.108862 [DOI: 10.1016/j.biopha.2019.108862]
Long JP, Dong LF, Chen FF, Fan YF (2019) miR-146a-5p targets interleukin-1 receptor-associated kinase 1 to inhibit the growth, migration, and invasion of breast cancer cells. Oncol Lett 17:1573–1580. https://doi.org/10.3892/ol.2018.9769 [DOI: 10.3892/ol.2018.9769]
McGuire A, Brown JA, Kerin MJ (2015) Metastatic breast cancer: the potential of miRNA for diagnosis and treatment monitoring. Cancer Metastasis Rev 34:145–155. https://doi.org/10.1007/s10555-015-9551-7 [DOI: 10.1007/s10555-015-9551-7]
Peng T et al (2019) The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma. Int J Oncol 55:657–670. https://doi.org/10.3892/ijo.2019.4837 [DOI: 10.3892/ijo.2019.4837]
Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641. https://doi.org/10.1016/j.cell.2009.02.006 [DOI: 10.1016/j.cell.2009.02.006]
Rizvi S, Gores GJ (2013) Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 145:1215–1229. https://doi.org/10.1053/j.gastro.2013.10.013 [DOI: 10.1053/j.gastro.2013.10.013]
Song Y et al (2015) GATA6 is overexpressed in breast cancer and promotes breast cancer cell epithelial-mesenchymal transition by upregulating slug expression. Exp Mol Pathol 99:617–627. https://doi.org/10.1016/j.yexmp.2015.10.005 [DOI: 10.1016/j.yexmp.2015.10.005]
Sorensen KP et al (2013) Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer. Breast Cancer Res Treat 142:529–536. https://doi.org/10.1007/s10549-013-2776-7 [DOI: 10.1007/s10549-013-2776-7]
Sun M, Kraus WL (2015) From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease. Endocr Rev 36:25–64. https://doi.org/10.1210/er.2014-1034 [DOI: 10.1210/er.2014-1034]
Tian F et al (2013) Aberrant expression of GATA binding protein 6 correlates with poor prognosis and promotes metastasis in cholangiocarcinoma. Eur J Cancer 49:1771–1780. https://doi.org/10.1016/j.ejca.2012.12.015 [DOI: 10.1016/j.ejca.2012.12.015]
Tian F et al (2017) miR-124 targets GATA6 to suppress cholangiocarcinoma cell invasion and metastasis. BMC Cancer 17:175. https://doi.org/10.1186/s12885-017-3166-z [DOI: 10.1186/s12885-017-3166-z]
Tyson GL, El-Serag HB (2011) Risk factors for cholangiocarcinoma. Hepatology 54:173–184. https://doi.org/10.1002/hep.24351 [DOI: 10.1002/hep.24351]
Uenishi T et al (2014) Proposal of a new staging system for mass-forming intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 21:499–508. https://doi.org/10.1002/jhbp.92 [DOI: 10.1002/jhbp.92]
Valle JW (2010) Advances in the treatment of metastatic or unresectable biliary tract cancer. Ann Oncol 21(Suppl 7):345–348. https://doi.org/10.1093/annonc/mdq420 [DOI: 10.1093/annonc/mdq420]
Wang D et al (2010) Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: from functions to targets. PloS one. https://doi.org/10.1371/journal.pone.0013067 [DOI: 10.1371/journal.pone.0013067]
Weber SM et al (2015) Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford) 17:669–680. https://doi.org/10.1111/hpb.12441 [DOI: 10.1111/hpb.12441]
Zhang RX, Zheng Z, Li K, Wu XH, Zhu L (2017) Both plasma and tumor tissue miR-146a high expression correlates with prolonged overall survival of surgical patients with intrahepatic cholangiocarcinoma. Medicine (Baltimore) 96:e8267. https://doi.org/10.1097/MD.0000000000008267 [DOI: 10.1097/MD.0000000000008267]
Zhang K, Chen J, Song H, Chen LB (2018) SNHG16/miR-140-5p axis promotes esophagus cancer cell proliferation, migration and EMT formation through regulating ZEB1. Oncotarget 9:1028–1040. https://doi.org/10.18632/oncotarget.23178 [DOI: 10.18632/oncotarget.23178]
Zhou C, Jiang CQ, Zong Z, Lin JC, Lao LF (2017) miR-146a promotes growth of osteosarcoma cells by targeting ZNRF3/GSK-3β/β-catenin signaling pathway. Oncotarget 8:74276–74286. https://doi.org/10.18632/oncotarget.19395 [DOI: 10.18632/oncotarget.19395]
Zhu Q et al (2019) Long non-coding RNA SNHG16 promotes proliferation and inhibits apoptosis of diffuse large B-cell lymphoma cells by targeting miR-497-5p/PIM1 axis. J Cell Mol Med 23:7395–7405. https://doi.org/10.1111/jcmm.14601 [DOI: 10.1111/jcmm.14601]

Grants

  1. CB2019152/the Scientific Research Plan of Hunan Provincial Health Commission

MeSH Term

Apoptosis
Bile Duct Neoplasms
Biomarkers, Tumor
Cell Movement
Cell Proliferation
Cholangiocarcinoma
GATA6 Transcription Factor
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs
Prognosis
RNA, Long Noncoding
Tumor Cells, Cultured

Chemicals

Biomarkers, Tumor
GATA6 Transcription Factor
GATA6 protein, human
MIRN146 microRNA, human
MicroRNAs
RNA, Long Noncoding
SNHG16 lncRNA, human
Journal Article

Word Cloud

Similar Articles

Cited By