Long non-coding RNA IRAIN suppresses apoptosis and promotes proliferation by binding to LSD1 and EZH2 in pancreatic cancer
- 562 Downloads
Long non-coding RNA (lncRNA) modulates gene expression, while lncRNA dysregulation is associated with human cancer. Furthermore, while recent studies have shown that lncRNA IRAIN plays an important role in other malignancies, the role of IRAIN in pancreatic cancer (PC) progression remains unclear. In this study, we found that upregulation of lncRNA IRAIN was significantly correlated with tumor size, TNM stage, and lymph node metastasis in a cohort of 37 PC patients. In vitro experiments showed that knockdown of IRAIN by small interfering RNA (siRNA) significantly induced cell apoptosis and inhibited cell proliferation in both BxPC-3 and PANC-1 cells. Further mechanism study showed that, by binding to histone demethylase lysine-specific demethylase 1 (LSD1), an enhancer of zeste homolog 2 (EZH2), IRAIN reduced PC tumor cell apoptosis and induced growth arrest by silencing the expression of Kruppel-like factor 2 (KLF2) and P15. Moreover, IRAIN expression was inversely correlated with that of KLF2 and P15 in PC tissues. To our knowledge, this is the first report elucidating the role and mechanism of IRAIN in PC progression.
KeywordsPancreatic cancer Apoptosis lncRNA IRAIN LSD1 EZH2
This work was supported by the Six Talents Peak Project of Jiangsu Province (WSN-050), the Key Project supported by Medical Science and Technology Development Foundation, Nanjing Department of Health (YKK13178), and the Medical Science and Technology Development Foundation, Nanjing Medical University (2014NJMUZD074).
Compliance with ethical standards
Informed consent was obtained from all patients. Our study was approved by the Research Ethics Committee of Nanjing Medical University, China.
Conflicts of interest
- 7.Lian, Y., et al., The long noncoding RNA HOXA transcript at the distal tip promotes colorectal cancer growth partially via silencing of p21 expression. Tumour Biol, 2015.Google Scholar
- 13.Zhou, Q., et al., Long noncoding RNA PVT1 modulates thyroid cancer cell proliferation by recruiting EZH2 and regulating thyroid-stimulating hormone receptor (TSHR). Tumour Biol, 2015.Google Scholar
- 14.Zang, C., et al., Long non-coding RNA LINC01133 represses KLF2, P21 and E-cadherin transcription through binding with EZH2, LSD1 in non small cell lung cancer. Oncotarget, 2016.Google Scholar
- 27.Zhang, Z.Y., et al., Loss of TINCR expression promotes proliferation, metastasis through activating EpCAM cleavage in colorectal cancer. Oncotarget, 2016.Google Scholar
- 31.Han, T., et al., EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer. Oncotarget, 2016.Google Scholar
- 32.Zhang, D., et al., KLF2 is downregulated in pancreatic ductal adenocarcinoma and inhibits the growth and migration of cancer cells. Tumour Biol, 2015.Google Scholar
- 34.Kaczynski J, Cook T, Urrutia R. Sp1- and Kruppel-like transcription factors. Genome Biol. 2003;4(2).Google Scholar