HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p
- 13 Downloads
The aberrant expression of highly upregulated in liver cancer (HULC) has been reported to participate in ovarian cancer development. A recent research has revealed that HULC-modulated microRNAs (miRNAs) in tumorigenesis. To confirm the functions of HULC on tumorigenesis of ovarian, we explored the effects of HULC expression on ovarian cancer cell development, as well as the underlying mechanism. We transfected SKOV3 cells with pEX-HULC, sh-HULC, and miR-125a-3p mimic as well as their corresponding negative controls (pEX-3, sh-NC, and NC) to alter the expression of HULC and miR-125a-3p, which were analyzed by quantitative reverse transcription PCR (qRT-PCR). Expression of proteins associated with cell cycle, apoptosis, and signaling pathways was determined by Western blot assay. The proliferation, apoptosis, migration, and invasion were explored by bromodeoxyuridine (BrdU) incorporation assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) method, and transwell migration and invasion assays, respectively. HULC overexpression promoted proliferation, migration, and invasion, while inhibited apoptosis of SKOV3 cells. In addition, HULC negatively regulated the expression of miR-125a-3p. Besides, miR-125a-3p mimic reversed the effects of HULC on proliferation, migration, and invasion as well as apoptosis of SKOV3 cells. Moreover, we found that HULC enhanced phosphorylated expression of regulatory factors in phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of rapamycin (PI3K/AKT/mTOR) signaling pathway by downregulating expression of miR-125a-3p. Overexpression of HULC promoted ovarian carcinoma development by activating PI3K/AKT/mTOR signaling pathway via downregulating miR-125a-3p.
KeywordsOvarian carcinoma HULC miR-125a-3p PI3K/AKT/mTOR signaling pathway
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
- 4.Gao N, Flynn DC, Zhang Z, Zhong XS, Walker V, Liu KJ, Shi X, Jiang BH (2004) G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Am J Physiol Cell Physiol 287:C281–C291. https://doi.org/10.1152/ajpcell.00422.2003 CrossRefGoogle Scholar
- 5.Gao Y, Meng H, Liu S, Hu J, Zhang Y, Jiao T, Liu Y, Ou J, Wang D, Yao L, Liu S, Hui N (2015) LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b. Hum Mol Genet 24:841–852. https://doi.org/10.1093/hmg/ddu502 CrossRefGoogle Scholar
- 9.Jiang L, Huang Q, Zhang S, Zhang Q, Chang J, Qiu X, Wang E (2010) Hsa-miR-125a-3p and hsa-miR-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells. BMC Cancer 10:318. https://doi.org/10.1186/1471-2407-10-318 CrossRefGoogle Scholar
- 13.Li SP, Xu HX, Yu Y, He JD, Wang Z, Xu YJ, Wang CY, Zhang HM, Zhang RX, Zhang JJ, Yao Z, Shen ZY (2016) LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway. Oncotarget 7:42431–42446. https://doi.org/10.18632/oncotarget.9883 Google Scholar
- 21.Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, Buck CR, Denk H, Schroeder R, Trauner M, Zatloukal K (2007) Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology 132:330–342. https://doi.org/10.1053/j.gastro.2006.08.026 CrossRefGoogle Scholar
- 25.Uzan VR, Lengert A, Boldrini E, Penna V, Scapulatempo-Neto C, Scrideli CA, Filho AP, Cavalcante CE, de Oliveira CZ, Lopes LF, Vidal DO (2016) High expression of HULC is associated with poor prognosis in osteosarcoma patients. PLoS One 11:e0156774. https://doi.org/10.1371/journal.pone.0156774 CrossRefGoogle Scholar
- 27.Wang Y, Chen F, Zhao M, Yang Z, Li J, Zhang S, Zhang W, Ye L, Zhang X (2017) The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186. J Biol Chem 292:15395–15407. https://doi.org/10.1074/jbc.M117.783738 CrossRefGoogle Scholar