scholarly journals NEDD4L-Induced Ubiquitination Mediated UBE2T Degradation Inhibits Progression of Lung Adenocarcinoma Via PI3K-AKT Signaling

2021 ◽  
Author(s):  
Yongbing Chen ◽  
Haihua Hong ◽  
Qingqing Wang ◽  
Junqiang Li ◽  
Wenfeng Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Half Life ◽  
Xenograft Model ◽  
E3 Ligase ◽  
Akt Signaling ◽  
Cell Counting ◽  
Downstream Signaling ◽  
Cell Progression

Abstract Background: Accumulating studies have indicated that Ubiquitin-conjugating enzyme E2T (UBE2T), as an oncogene, promotes progression and metastasis of lung cancer, including lung adenocarcinoma (LUAD), but it is completely unknown whether and how UBE2T is ubiquitylated and degraded, and by which E3 ligase. Methods: The relationship NEDD4L with UBE2T in LUAD tissues and cells was found by bioinformatic analyses and immunoblotting. Cell counting kit-8, colony formation assay, half-life analysis and the in vivo ubiquitylation assay, generation of xenograft model were performed to determine how NEDD4L regulates UBE2T and its downstream signaling pathway in vitro and in vivo.Results: Bioinformatic analyses found that NEDD4L, as a potential correlation E3 ligase of UBE2T, was negatively correlated with UBE2T in LUAD. Consistently, UBE2T protein half-life was shortened or extended by NEDD4L overexpression or depletion, respectively. NEDD4L against LUAD cell progression in vitro and in vivo via inducing the ubiquitination-mediated UBE2T degradation, which repressed PI3K-AKT signaling. Similarly, NEDD4L predicted a better patient survival, whereas UBE2T predicted a worse survival.Conclusions: Collectively, our study reveals that NEDD4L is a novel E3 ligase of UBE2T for targeted ubiquitination and degradation, and results in repressing PI3K-AKT signaling, which can inhibit LUAD cell progression.

scholarly journals NEDD4L-induced ubiquitination mediating UBE2T degradation inhibits progression of lung adenocarcinoma via PI3K-AKT signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yongbing Chen ◽  
Haihua Hong ◽  
Qingqing Wang ◽  
Junqiang Li ◽  
Wenfeng Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Half Life ◽  
Critical Role ◽  
E3 Ligase ◽  
Akt Signaling ◽  
Cell Counting ◽  
Cell Progression ◽  
The Relationship

Abstract Background A number of studies have indicated that Ubiquitin-conjugating enzyme E2T (UBE2T), as an oncogene, promotes progression and metastasis of lung cancer, including lung adenocarcinoma (LUAD), but it is completely unknown whether and how UBE2T is ubiquitylated and degraded, and by which E3 ligase. NEDD4L plays a critical role in the regulation of cellular processes of various cancers, most of which is attributed to its E3 ubiquitin ligase function. However, the relationship between NEDD4L and UBE2T in LUAD has not been elucidated. Methods The relationship between NEDD4L and UBE2T in LUAD tissues and cells was found by bioinformatic analyses and immunoblotting. Cell counting kit-8, colony formation assay, half-life analysis and the in vivo ubiquitylation assay, generation of xenograft model were performed to determine how NEDD4L regulates UBE2T and its downstream signaling pathway in vitro and in vivo. Results Bioinformatic analyses found that NEDD4L, as a potential correlation E3 ligase of UBE2T, was negatively correlated with UBE2T in LUAD. Consistently, UBE2T protein half-life was shortened or extended by NEDD4L overexpression or depletion, respectively. NEDD4L inhibited LUAD cell progression in vitro and in vivo via inducing the ubiquitination-mediated UBE2T degradation, which repressed PI3K-AKT signaling. Similarly, NEDD4L predicted a better patient survival, whereas UBE2T predicted a worse survival. Conclusions Collectively, our results reveal that NEDD4L is a novel E3 ligase of UBE2T, which can inhibit PI3K-AKT signaling by targeting for UBE2T ubiquitination and degradation, resulting in repression of LUAD cell progression.

scholarly journals LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 871-883
Author(s):  
Jinshan Zhang ◽  
Dan Rao ◽  
Haibo Ma ◽  
Defeng Kong ◽  
Xiaoming Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

scholarly journals LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Gege Shu ◽  
Huizhao Su ◽  
Zhiqian Wang ◽  
Shihui Lai ◽  
Yan Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Mechanism Study ◽  
Downstream Signaling ◽  
Mouse Xenograft Model ◽  
High Level

Abstract Background Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. Methods QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study. Results We found that LINC00680 was remarkably upregulated in HCC tissues. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K. Conclusion LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.

scholarly journals Silencing VEGF enhances the radiosensitivity of the radioresistant human nasopharyngeal carcinoma cell line CNE-2R by inhibiting autophagy through the activation of mTOR pathway

2020 ◽  
Author(s):  
Li Chen ◽  
Guoxiang Lin ◽  
Kaihua Chen ◽  
Fangzhu Wan ◽  
Yongchu Sun ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nasopharyngeal Carcinoma ◽  
Cell Line ◽  
Western Blotting ◽  
Xenograft Model ◽  
Mtor Pathway ◽  
Angiogenic Factor ◽  
Cell Counting

Abstract Background: Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. VEGF was reported to promote the occurrence of autophagy, which enhanced to the radioresistance of tumors. The purpose of our study was to investigate the influence of VEGF silencing on the radiosensitivity of nasopharyngeal carcinoma radioresistant cell line CNE-2R and the underlying mechanisms.Methods: The radiosensitivity of CNE-2R cells after silencing VEGF was detected by cell counting kit 8 (CCK-8) and clonogenic assay, cell cycle and apoptosis was subjected to flow cytometry. DNA damage and autophagy were observed by immunofluorescence and western blotting. The interaction between VEGF and mTOR was confirmed by western blotting and co-immunoprecipitation analysis. In vivo, the effect of VEGF on radiosensitivity of NPC cells was investigated through xenograft model, furthermore, immunohistochemistry and TUNEL assay were used to further verify the relationship between autophagy and radiosensitivity in NPC after VEGF depletion.Results: Downregulation of VEGF significantly inhibited cell proliferation and induced apoptosis of CNE-2R cells after radiotherapy in vitro and in vivo. In addition, VEGF knockdown not only decreased autophagy level, but also delayed the DNA damage repair in CNE-2R cells after irradiation. Mechanistically, silencing VEGF suppressed autophagy through the activation of mTOR pathway.Conclusion: VEGF depletion increased radiosensitivity of NPC radioresistant cell CNE-2R by suppressing autophagy via the activation of mTOR pathway.

scholarly journals LINC00152 down-regulated miR-193a-3p to enhance MCL1 expression and promote gastric cancer cells proliferation

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Yong Huang ◽  
Hui Luo ◽  
Fang Li ◽  
Yun’e Yang ◽  
Guangsheng Ou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Xenograft Model ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Mouse Xenograft Model ◽  
Vitro Effect

The present work aimed to probe into the effect of long non-coding RNA (lncRNA) LINC00152 on gastric cancer (GC) cells proliferation by regulating miR-193a-3p and its target gene MCL1. Transfected si-LINC00152 was used to down-regulate LINC00152, and cells proliferation was measured by the cell counting kit-8 (CCK-8) assay. Cell apoptosis and cell cycle were analyzed by flow cytometry (FCM). Besides, we also detected the potential functional effects of differential expression of LINC00152 in vivo using nude mouse xenograft model. We overexpressed and downexpressed miR-193a-3p to study the in vitro effect of miR-193a-3p on GC cells proliferation and vitality. And MCL1 was silenced by shRNA to investigate the effect of MCL1 on proliferation of GC cells. In this research, LINC00152 was proven to have a higher expression level in GC tissues than in the adjacent normal tissues. GC cells proliferation was inhibited after LINC00152 was down-regulated. LINC00152 inhibited the expression of miR-193a-3p, which negatively regulated MCL1. In addition, GC cells proliferation was inhibited by cell transfection with shRNA-MCL1, and enhanced by transfection with miR-193a-3p mimics. Our study suggested that LINC00152 was overexpressed in GC tissues, and it down-regulated miR-193a-3p to enhance MCL1 expression thereby promoting GC cells proliferation.

scholarly journals Curcumol inhibits lung adenocarcinoma growth and metastasis via inactivation of PI3K/AKT and Wnt/ß-catenin pathway

2020 ◽  
Author(s):  
Sheng Li ◽  
Guoren Zhou ◽  
Wei Liu ◽  
Jinjun Ye ◽  
Fangliang Yuan ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Lung Metastasis ◽  
Molecular Mechanisms ◽  
Lung Tumor ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Medical Plant ◽  
Rhizoma Curcumae

Curcumol (Cur), isolated from the Traditional Chinese Medical plant Rhizoma Curcumae, is the bioactive component of sesquiterpene reported to possess anti-tumor activity. However, its bioactivity and mechanisms against lung adenocarcinoma are still unclear. We investigated its effect on lung adenocarcinoma and elucidated its underlying molecular mechanisms. <I>In vitro</I>, Cur effectively suppressed proliferation, migration and invasion of lung adenocarcinoma cells A549 and H460, which were associated with the altered expressions of signaling molecules, including p-AKT, p-PI3K, p-LRP5/6, AXIN, APC, GSK3 &szlig; and p- &szlig;-catenin, matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, Cur significantly induced cell apoptosis of A549 and H460 by promoting the expression of Bax, caspase-3 and caspase-9 and suppressing the expression of Bcl-2, and arrested the cell cycle at the G0/G1 phase by lowering the levels of cyclin D1, CDK1 and CDK4. In vivo experiment revealed that Cur could inhibit lung tumor growth and lung metastasis, which were consistent with these in vitro results. In xenograft model mice, Cur strongly decreased tumor weight and tumor volume, which may were related to the down-regulation of p-AKT and p-PI3K by immunofluorescence analysis. In addition, lung metastasis model experiment suggested that Cur dramatically decreased the ratio of lung/total weight, tumor metastatic nodules, and the expressions of MMP-2 and MMP-9 in lung tissues compared with the control. Overall, these data suggested that the inhibitory activity of Cur on lung adenocarcinoma via the inactivation of PI3K/Akt and Wnt/ &szlig;-catenin pathways, at least in part, indicating that curcumol may be a potential anti-tumor agent for lung adenocarcinoma therapy.

Evaluation of Pharmacokinetic-Pharmacodynamic (PKPD) Relationship of an Oral, Selective, First-in-Class, Potent IDH2 Inhibitor, AG-221, from a Phase 1 Trial in Patients with Advanced IDH2 Mutant Positive Hematologic Malignancies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3737-3737 ◽  
Author(s):  
Bin Fan ◽  
Yue Chen ◽  
Fang Wang ◽  
Katharine Yen ◽  
Luke Utley ◽  
...  
Keyword(s):  
Mouse Model ◽  
Phase I ◽  
Half Life ◽  
Phase I Study ◽  
Xenograft Model ◽  
Hematologic Malignancies ◽  
Plasma Exposure ◽  
Xenograft Mouse Model

Abstract Introduction: Isocitrate dehydrogenase (IDH) is a critical enzyme in the citric acid cycle, catalyzing the oxidative decarboxylation of isocitrate to produce alpha-ketoglutarate (a-KG). The mutant IDH are not catalytically inactive enzymes, but rather possess novel enzymatic activities, catalyzing the reduction of α-KG to the ‘oncometabolite' 2-hydroxyglutarate (2-HG), which has been found to be elevated in patients with several tumor types, including acute myelogenous leukemia (AML). AG-221 is an oral, selective, first-in class, potent inhibitor of the IDH2 mutant protein. The compound has been demonstrated to reduce 2-HG levels by >90% and reverse histone and DNA hypermethylation in vitro, and to induce differentiation in leukemia cell models. In vivo pharmacokinetic/pharmacodynamic (PK/PD) studies in a U87MG IDH2 (R140Q) xenograft mouse model demonstrated robust plasma 2-HG lowering, and the correlation between PK (AG-221 exposure) and PD (the inhibition of 2-HG production) was used for human efficacious exposure projection. The PK/PD correlation was further confirmed in a primary human AML xenograft model in mice. These results are compared to early PK/PD results from the ongoing first-in-human Phase I study of AG-221 in patients with advanced IDH2 mutant positive hematologic malignancies [NCT01915498]. Methods: This first-in-man Phase I study of oral AG-221 was designed to evaluate the safety, PK, and PD, including 2-HG levels, as well as clinical activity. AG-221 was administered orally once (QD) or twice (BID) per day in continuous 28-day cycles. Sequential cohorts of patients were enrolled at higher dose levels. Patients included in this analysis were enrolled to doses of 30, 50, 75 mg BID and 100 mg QD (total N=21). Patients bearing the two dominant IDH2 mutations, R140Q (85.7%) or R172K (14.3%), were enrolled in the Phase I study. Blood was collected at multiple time points for determination of the PK and PD effects of AG-221. The concentrations of AG-221and 2-HG in plasma samples were determined using a qualified LC-MS/MS based method. PK and PK/PD analyses were performed using WinNonLin®. In addition, PK/PD relationships and efficacy of AG-221 was evaluated in a U87MG IDH2-R140Q xenograft mouse model and a primary human AML xenograft mouse model carrying the IDH2-R140Q mutation following oral doses. Results: Preliminary analysis of PK demonstrated excellent oral AG-221 exposure in humans. The mean plasma half-life is greater than 40 hours. Plasma 2-HG concentrations decreased rapidly; substantial and constant plasma 2-HG inhibition was achieved following multiple AG-221 doses in patients, and the inhibition was dose and drug exposure dependent. Based on exposure-response analyses with R140Q patients, the AG-221 AUC0-10hr value of 47.1 hr•ug/mL is estimated to result in sustained 90% plasma 2-HG inhibition in human (Figure1) which is associated with IC90 of 66 ng/mL. This is consistent with an in vivo IC90 in an AML xenograft model, U87MG IDH2-R140Q. In addition, up to 50% plasma 2-HG inhibition was observed in limited number of patients with R172K mutation. Figure 1. AG-221 plasma exposure and 2-HG inhibition correlation in patients with IDH2-R140Q mutation Figure 1. AG-221 plasma exposure and 2-HG inhibition correlation in patients with IDH2-R140Q mutation Conclusions: The pharmacokinetic profile for AG-221 supports QD dosing based on the high plasma exposure and long half-life observed in this study. AG 221 suppressed the production of 2-HG in plasma to the normal range found in healthy volunteers. 2-HG inhibition in R140Q mutation was translated well from mice to humans as well as from in vitro to in vivo. Disclosures Fan: Agios Pharmaceuticals: Employment, Stockholder Other. Chen:Agios Pharmaceuticals: Employment, Stockholder Other. Wang:Agios Pharmaceuticals: Employment, Stockholder Other. Yen:Agios: Employment. Utley:Agios Pharmaceuticals: Employment, Stockholder Other. Almon:Agios Pharmaceuticals: Employment, Stockholder Other. Biller:Agios Pharmaceuticals: Employment, Stockholder Other. Agresta:Agios Pharmaceuticals: Employment, Stockholder Other. Yang:Agios Pharmaceuticals: Employment, Stockholder Other.

scholarly journals Ganoderma tsugaeInduces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Yang-Hao Yu ◽  
Han-Peng Kuo ◽  
Hui-Hsia Hsieh ◽  
Jhy-Wei Li ◽  
Wu-Huei Hsu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
S Phase ◽  
Akt Signaling Pathway ◽  
Suppression Effect ◽  
Phase Arrest ◽  
S Phase Arrest

Ganoderma tsugae(GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cellsin vitroandin vivoand sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.

scholarly journals ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Weijie Zhang ◽  
Ruochen Zhang ◽  
Yuanyuan Zeng ◽  
Yue Li ◽  
Yikun Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Nuclear Translocation ◽  
E3 Ligase ◽  
Migration And Invasion ◽  
Drug Candidate ◽  
Proliferation And Metastasis

AbstractLung cancer is recognized as the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype, accounting for approximately 85% of lung cancer cases. Although great efforts have been made to treat lung cancer, no proven method has been found thus far. Considering β, β-dimethyl-acryl-alkannin (ALCAP2), a natural small-molecule compound isolated from the root of Lithospermum erythrorhizon. We found that lung adenocarcinoma (LUAD) cell proliferation and metastasis can be significantly inhibited after treatment with ALCAP2 in vitro, as it can induce cell apoptosis and arrest the cell cycle. ALCAP2 also significantly suppressed the volume of tumours in mice without inducing obvious toxicity in vivo. Mechanistically, we revealed that ALCAP2-treated cells can suppress the nuclear translocation of β-catenin by upregulating the E3 ligase NEDD4L, facilitating the binding of ubiquitin to β-catenin and eventually affecting the wnt-triggered transcription of genes such as survivin, cyclin D1, and MMP9. As a result, our findings suggest that targeting the oncogene β-catenin with ALCAP2 can inhibit the proliferation and metastasis of LUAD cells, and therefore, ALCAP2 may be a new drug candidate for use in LUAD therapeutics.

Silencing of Long Noncoding RNA LINC01132 Alleviates the Oncogenicity of Epithelial Ovarian Cancer by Regulating the microRNA-431-5p/SOX9 Axis

2021 ◽  
Author(s):  
Wei Zhu ◽  
Xiangming Xiao ◽  
Jinqin Chen
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Molecular Events

Abstract Background: To date, long intergenic nonprotein coding RNA 1132 (LINC01132) expression in epithelial ovarian cancer (EOC) and the underlying mechanisms have not been explored. In this study, we measured LINC01132 expression in EOC and assessed the effects of LINC01132 on the malignant behaviours of EOC cells in vitro and in vivo. Additionally, mechanistic studies were performed to elucidate the molecular events that occurred downstream of LINC01132 in EOC cells. Methods: Reverse-transcription quantitative PCR (RT-qPCR) was utilized to verify LINC01132 expression in EOC. The effects of LINC01132 on the malignant behaviours of EOC cells were determined using a Cell Counting Kit-8 assay, flow cytometry analysis, cell migration and invasion assays and a tumour xenograft model. The targeting interaction among LINC01132, microRNA-431-5p (miR-431-5p) and SRY-Box 9 (SOX9) was verified by RNA immunoprecipitation and luciferase reporter assays. Results: LINC01132 was overexpressed in EOC and was obviously associated with poor patient prognosis. Functionally, cell experiments revealed that LINC01132 depletion could inhibit EOC cell proliferation, migration and invasion and promote cell apoptosis in vitro. Additionally, loss of LINC01132 attenuated tumour growth in vivo. Mechanistically, LINC01132 acted as a competing endogenous RNA by sequestering miR-431-5p and thereby increasing SOX9 expression in EOC cells, forming a LINC01132/miR-431-5p/SOX9 axis. In rescue experiments, miR-431-5p inhibition or SOX9 re-expression eliminated the inhibitory effects of LINC01132 silencing on the pathological behaviours of EOC cells. Conclusions: Generally, LINC01132 exhibited oncogenic activities in EOC cells in vitro and in vivo by regulating the outcome of the miR-431-5p/SOX9 axis, providing an effective target for EOC diagnosis, therapy and prognosis evaluation.

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