Expression of Concern: LncRNA TUG1 facilitates proliferation, invasion and stemness of ovarian cancer cell via miR‐186‐5p/ZEB1 axis

Abstract

LncRNA TUG1 has been rarely studied in ovarian cancer (OC), our objective was to explore the role of TUG1 in the regulation of malignant phenotypes of OC. Vectors of sh-TUG1, miR-186-5p and pcDNA-ZEB1 were, respectively, constructed and used to infect OC cells. MTT and transwell assays were applied for representing cell proliferation and invasion, respectively. Sphere formation experiment was used to detect the stemness of OC cells. Western blotting and qRT-PCR were employed for detecting the expression of multiple biomarkers on protein and RNA levels, respectively. The luciferase assay was performed to reveal the interactions between miR-186-5p and TUG1 or ZEB1. The silencing of TUG1 and upregulation of miR-186-5p both suppressed the cell proliferation, invasion and cancer stem cell (CSC) properties. Additionally, luciferase assay verified that miR-186-5p directly binds TUG1 and ZEB1. Moreover, overexpression of ZEB1 rescued the impact on the proliferation, invasion and stemness of TUG1 silencing in OC. TUG1 sponges miR-186-5p to release ZEB1 and promotes the proliferation, invasion and stemness of OC cells, suggesting that TUG1 could be a potential therapeutic target for OC therapy. Significance of the study: LncRNA TUG1 could promote proliferation, invasion and stemness of ovarian cancer cells. Our study first discovered that TUG1 play a tumourigenic role in ovarian cancer by regulating stemness of cancer cells. Mechanism research exhibited the regulation role of TUG1 in ovarian cancer cells was miR-186-5p/ZEB1 axis depended. These results provided a new perspective to understand the pathogenesis and development of ovarian cancer; it will offer new evidence for better diagnosis and treatment therapy of ovarian cancer.

Long non-coding RNA TUG1/microRNA-187-3p/TESC axis modulates progression of pituitary adenoma via regulating the NF-κB signaling pathway

“…In addition, evidence in our research revealed that the inhibited TUG1 and elevated miR-187-3p were able to restrain the growth of PA cells. In line with this result, Hui et al 37 have verified that TUG1 inhibition could block the cell cycle and suppress the proliferation of pancreatic cancer cells, and it has been demonstrated that TUG1 facilitates the proliferation and stemness of ovarian cancer cells 38 . As for the role of miR-187-3p, Chen et al 39 have figured out that the overexpressed miR-187 has the ability to repress proliferation of gastric cancer cells and arrest the gastric cancer cells at the G0/G1 phase.…”

LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms

“…For the lncRNA TUG1 (taurine upregulated gene 1), the ceRNA mode of action was established in OvCa in four works published in 2020 [ 177 , 178 , 179 , 180 ]. In all these studies, TUG1 was upregulated in OvCa, and this oncogenic lncRNA was associated with cell migration, invasion, and metastasis ( Table 2 ).…”

“…Direct interactions in the axis TUG1/miR-29b-3p/MDM2 (mouse double minute 2 homolog: a proto-oncogene, encoding a nuclear-localized E3 ubiquitin ligase) [ 177 , 178 ] were confirmed by luciferase reporter and RIP assays. TUG1/miR-186-5p/ZEB1 (zinc finger E-box-binding homeobox 1, EMT-related transcription factor) and TUG1/miR-1299/NOTCH3 (notch receptor 3) axes were also verified using luciferase reporter assays [ 179 , 180 ]. The authors observed that MDM2, as the primary negative regulatory factor of the p53 protein, decreases the phosphorylation level of p53.…”

“…In addition, it was revealed that TUG1, by targeting miR-29b-3p, induces autophagy and consequently results in paclitaxel-resistance and poorer prognosis in OvCa patients [ 178 ]. A more detailed investigation of sphere formation and cancer stem cell properties revealed the ability of TUG1 to increase the stemness of OvCa cells, at least in part through the activation of the target ZEB1 [ 179 ]. Besides, TUG1 was found to be a potential downstream target of NOTCH3, forming a miR-1299/NOTCH3/TUG1 feedback loop in the development of OvCa.…”

“…Besides, TUG1 was found to be a potential downstream target of NOTCH3, forming a miR-1299/NOTCH3/TUG1 feedback loop in the development of OvCa. Therefore, three axes were identified and involvement of TUG1 in proliferation, migration, invasion, and metastasis was demonstrated in vitro and in vivo but, in addition, the participation of TUG1 in the increase in chemoresistance and stemness of OvCa cells and the formation of a feedback loop for the TUG1/miR-1299/NOTCH3 axis is shown in the cited works [ 177 , 178 , 179 , 180 ].…”