Long non-coding RNA NEAT1 facilitates the growth, migration, and invasion of ovarian cancer cells via the let-7 g/MEST/ATGL axis

Abstract Background/Aim Growing evidence indicates a significant role of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in ovarian cancer, a frequently occurring malignant tumor in women; however, the possible effects of an interplay of NEAT1 with microRNA (miRNA or miR) let-7 g in ovarian cancer are not known. The current study aimed to investigate the role of the NEAT1/let-7 g axis in the growth, migration, and invasion of ovarian cancer cells and explore underlying mechanisms. Methods NEAT1 expression levels were examined in clinical tissue samples and cell lines. The relationships between NEAT1, let-7 g, and MEST were then analyzed. Gain- or loss-of-function approaches were used to manipulate NEAT1 and let-7 g. The effects of NEAT1 on cell proliferation, migration, invasion, and apoptosis were evaluated. Mouse xenograft models of ovarian cancer cells were established to verify the function of NEAT1 in vivo. Results NEAT1 expression was elevated while let-7 g was decreased in ovarian cancer clinical tissue samples and cell lines. A negative correlation existed between NEAT1 and let-7 g, whereby NEAT1 competitively bound to let-7 g and consequently down-regulate let-7 g expression. By this mechanism, the growth, migration, and invasion of ovarian cancer cells were stimulated. In addition, let-7 g targeted mesoderm specific transcript (MEST) and inhibited its expression, leading to promotion of adipose triglyceride lipase (ATGL) expression and inhibition of ovarian cancer cell growth, migration, and invasion. However, the effect of let-7 g was abolished by overexpression of MEST. Furthermore, silencing of NEAT1 decreased the xenograft tumor growth by decreasing MEST while up-regulating let-7 g and ATGL. Conclusions Cumulatively, the findings demonstrated that NEAT1 could promote malignant phenotypes of ovarian cancer cells by regulating the let-7 g/MEST/ATGL signaling axis. Therefore, NEAT1 can be regarded as an important molecular target and biomarker for ovarian cancer.

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Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02274-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Qingjuan Meng ◽

Ningning Wang ◽

Guanglan Duan

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Invasion And Migration ◽

Non Coding Rna ◽

And Migration ◽

Long Non Coding Rna

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

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Long non‑coding RNA FOXD2‑AS1 promotes proliferation, migration and invasion of ovarian cancer cells via regulating the expression of miR‑4492

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.9738 ◽

2021 ◽

Vol 21 (4) ◽

Author(s):

Jianfen Gao ◽

Faqin Liu ◽

Xia Zhao ◽

Ping Zhang

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Non Coding Rna ◽

Long Non Coding Rna

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Knockdown of long non‑coding RNA LINC00152 increases cisplatin sensitivity in ovarian cancer cells

Experimental and Therapeutic Medicine ◽

10.3892/etm.2019.8066 ◽

2019 ◽

Cited By ~ 3

Author(s):

Hanxue Zou ◽

Hongxia Li

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Non Coding Rna ◽

Cisplatin Sensitivity ◽

Long Non Coding Rna

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Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1 in human ovarian cancer cells

Neoplasma ◽

10.4149/neo_2015_051 ◽

2015 ◽

Vol 62 (03) ◽

pp. 432-438 ◽

Cited By ~ 67

Author(s):

F. WANG ◽

J. ZHOU ◽

X. XIE ◽

J. HU ◽

L. CHEN ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cisplatin Resistance ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Non Coding Rna ◽

Long Non Coding Rna

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MicroRNA-30 inhibits the growth of human ovarian cancer cells by suppressing RAB32 expression

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211058642 ◽

2022 ◽

Vol 36 ◽

pp. 205873842110586

Author(s):

Yan Zhang ◽

Min Zhou ◽

Kun Li

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Luciferase Assay ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Transcriptional Level ◽

Human Ovarian Cancer ◽

Mesenchymal Transition

Introduction MicroRNAs (miRs) exhibit the potential to act as therapeutic targets for the management of human cancers including ovarian cancer. The role of microRNA-30 (miR-30) via modulation of RAB32 expression has not been studied in ovarian cancer. Consistently, the present study was designed to characterize the molecular role of miR-30/RAB32 axis in human ovarian cancer. Methods Cell viability was determined by MTT assay. Expression analysis was carried out by qRT-PCR. Dual luciferase assay was used to confirm the interaction between miR-30 and RAB32. Scratch-heal and transwell chamber assays were used to monitor the cell migration and invasion. Western blotting and immunofluorescence assays were used to determine the protein expression. Results The results revealed significant ( p < 0.05) downregulation of miR-30 in human ovarian cancer cell lines. Overexpression of miR-30 in ovarian SK-OV-3 and A2780 cancer cells significantly ( p < 0.05) inhibited their proliferation. Besides, ovarian cancer cells overexpressing miR-30 showed significantly ( p < 0.05) lower migration and invasion. The miR-30 upregulation also altered the expression pattern of marker proteins of epithelial–mesenchymal transition in ovarian cancer cells. In silico analysis predicted RAB32 as the molecular target of miR-30 at post-transcriptional level. The silencing of RAB32 mimicked the tumor-suppressive effects of miR-30 overexpression in ovarian cancer cells. Nonetheless, overexpression of RAB32 could prevent the tumor-suppressive effects of miR-30 on SK-OV-3 and A2780 cancer cells. Conclusion Taken together, the results suggest the tumor-suppressive role of miR-30 and point towards the therapeutic utility of miR-30/RAB32 molecular axis in the management of ovarian cancer

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Long Non-coding RNA CCAT1 Sponges miR-454 to Promote Chemoresistance of Ovarian Cancer Cells to Cisplatin by Regulation of Surviving

Cancer Research and Treatment ◽

10.4143/crt.2019.498 ◽

2020 ◽

Vol 52 (3) ◽

pp. 798-814 ◽

Cited By ~ 3

Author(s):

De-Ying Wang ◽

Na Li ◽

Yu-Lan Cui

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cell Line ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Qrt Pcr ◽

Non Coding Rna ◽

Induced Apoptosis ◽

Long Non Coding Rna

PurposeColon cancer-associated transcript 1 (CCAT1) was identified as an oncogenic long non-coding RNA (lncRNA) in a variety of cancers. However, there was a lack of understanding of the mechanism by which CCAT1 conferred cisplatin (also known as DDP) resistance in ovarian cancer cells.Materials and MethodsCell viability of A2780, SKOV3, A2780/DDP, and SKOV3/DDP cells upon cisplatin treatment was monitored by MTT assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression levels of CCAT1 and miR-454. The effect of sh-CCAT1 on cisplatin response was investigated in xenografts study. Bioinformatic analysis, luciferase reporter assay and qRT-PCR were conducted to validate the direct interaction among CCAT1, miR-454, and survivin. Apoptosis was determined by flow cytometry after dual staining of Annexin-V-FITC/propidium iodide, and the expression of apoptosis-related proteins Bcl-2, Bax and survivin were detected by qRT-PCR and Western blotting. Xenograft study was conducted to monitor in vivo tumor formation.ResultsCCAT1 was highly expressed in cisplatin-resistant ovarian cancer cell line A2780/DDP and SKOV3/DDP. Knockdown of CCAT1 restored sensitivity to cisplatin in vitro and in vivo. Our data revealed that silencing of CCAT1 promoted cisplatin-induced apoptosis via modulating the expression of pro- or anti-apoptotic proteins Bax, Bcl-2, and survivin. CCAT1 directly interacted with miR-454, and miR-454 overexpression potentiated cisplatin-induced apoptosis. Survivin was identified as a functional target of miR-454, restoration of survivin attenuated the effect of miR-454 on cisplatin response. In addition, miR-454 inhibitor or overexpression of survivin was found to abolish sh-CCAT1–induced apoptosis upon cisplatin treatment.ConclusionCCAT1/miR-454/survivin axis conferred cisplatin resistance in ovarian cancer cells.

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Interference of long non‑coding RNA HAGLROS inhibits the proliferation and promotes the apoptosis of ovarian cancer cells by targeting miR‑26b‑5p

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.10311 ◽

2021 ◽

Vol 22 (2) ◽

Author(s):

Lin Zhu ◽

Mei Mei

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Non Coding Rna ◽

Long Non Coding Rna

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UBE2S promotes the progression and Olaparib resistance of ovarian cancer through Wnt/β-catenin signaling pathway

Journal of Ovarian Research ◽

10.1186/s13048-021-00877-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Wenjing Hu ◽

Min Li ◽

Youguo Chen ◽

Xinxian Gu

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Xenograft Model ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Cancer Proliferation ◽

Skov3 Cells

Abstract Background Ovarian cancer is the most lethal gynecologic malignancy worldwide. Olaparib, an inhibitor of poly (ADP-ribose) polymerase (PARP), is becoming widely used in ovarian cancer treatment. The overall survival of ovarian cancer has not been significantly changed over the past decades and ovarian cancer has become increasingly resistant to the Olaparib. Ubiquitin-conjugating enzyme E2S (UBE2S) has been proved to promote malignant behaviors in many cancers. However, the function of UBE2S in the development and Olaparib resistance of ovarian cancer are unclear. Materials and methods In this study, we detected the expression of UBE2S in normal fallopian tube (FT) and HGSOC tissues. A2780 and SKOV3 cells were stably transfected with PCMV-UBE2S, PCMV-UBE2S-C95S, UBE2S shRNAs, and negative controls. The CCK8 assay and clonogenic assay were conducted to analyze ovarian cancer proliferation and Olaparib resistance. The transwell assay was performed to determine the migration and invasion of ovarian cancer cells. The relative protein levels of the Wnt/β-catenin signaling pathway were tested using western blot. The ovarian cancer cells were treated with XAV-939 to investigate the role of Wnt/β-catenin signaling pathway in Olaparib resistance. Moreover, we repeated some above procedures in the xenograft model. Results The results demonstrated that UBE2S was highly upregulated in HGSOC and that high UBE2S expression was correlated with poor outcomes in HGSOC. UBE2S promoted ovarian cancer proliferation and drived the migration and invasion of ovarian cancer cells. UBE2S activated the Wnt/β-catenin signaling pathway in ovarian cancer resulting in Olaparib resistance in vitro and in vivo. Furthermore, UBE2S enhanced the proliferation and Olaparib resistance of ovarian cancer in its enzymatic activity dependent manner. Conclusions These data suggest a possible molecular mechanism of proliferation and metastasis of ovarian cancer and highlight the potential role of UBE2S as a therapeutic target in ovarian cancer.

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ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2

Chemotherapy ◽

10.1159/000493864 ◽

2018 ◽

Vol 63 (5) ◽

pp. 262-271 ◽

Cited By ~ 10

Author(s):

Yajie Cui ◽

Li Qin ◽

Defu Tian ◽

Ting Wang ◽

Lijing Fan ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Tumor Development ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Cell Surface Molecule ◽

Important Regulator ◽

Induced Apoptosis

Ovarian cancer is one of the deadliest gynecological malignancies in women. Chemoresistance has been a major obstacle for ovarian cancer treatment. Zinc finger E-box-binding homeobox 1 (ZEB1) is an important regulator of tumor development in various types of cancer. Abnormal expression of SLC3A2 (CD98hc), a type 2 transmembrane cell surface molecule, has been described in several cancers. This study was designed to investigate the role of ZEB1 and SLC3A2 in the chemoresistance to cisplatin in ovarian cancer cells. We found that ZEB1 was increased in cisplatin-resistant SKOV3/DPP cells. Downregulation of ZEB1 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. In addition, downregulation of ZEB1 decreased the volume and weight of implanted tumors. SLC3A2 was decreased in cisplatin-resistant SKOV3/DPP cells. Upregulation of SLC3A2 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. Moreover, upregulation of SLC3A2 decreased the volume and weight of implanted tumors. Downregulation of ZEB1 resulted in a significant increase of SLC3A2 expression. Moreover, downregulation of SLC3A2 significantly inhibited ZEB1 knockdown-mediated inhibition of cisplatin-resistance. ZEB1-mediated regulation of SLC3A2 was involved in the chemoresistance to cisplatin in ovarian cancer cells. Overall, we provide new insights into the mechanism of chemoresistance to cisplatin in ovarian cancer cells. ZEB1/SLC3A2 may be promising therapeutic targets for enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.

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