LncRNA LINC00665 Promotes Ovarian Cancer Cell Proliferation and Inhibits Apoptosis via Targeting MiR-181a-5p/FHDC

Abstract Objective: Previous reports indicate that long intergenic non-coding RNA LINC00665 naturally occurred vital effect in various cancers. Herein, the role of LINC00665 in ovarian cancer progress was explored.Methods: We found that LINC00665 was upregulated in ovarian cancer cell lines. Besides that, A series of assays including flow cytometry, wound-healing, Transwell, Cell Counting Kit-8 (CCK-8), and EdU assay confirmed that the knockdown of LINC00665 could reduce the viability, proliferation and migration of SKOV-3 and OVCAR-3 cells. Accumulating evidence indicates that many lncRNAs can function as endogenous miRNA sponges by competitively binding common miRNAs. In this study, the bioinformatics analysis suggested that LNC00665 specifically binds to miR-181a-5p.Results: LINC00665 downregulated the miR-181a-5p in SKOV-3 and OVCAR-3 cells. The knockdown of miR-181a-5p evidently reverses the inhibitory effect of sh-LINC00662. Besides, FH2 Domain Containing 1 (FHDC1) has been proved to deed as an effective target of miR-181a-5p.Conclusion: Our results reveal the knockdown of LINC00665 facilitates ovarian cancer via development by sponging miR-181a-5p and upregulating FHDC1 expression; these may contribute to ovarian cancer therapy.

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LncRNA LINC00665 promotes ovarian cancer cell proliferation and inhibits apoptosis via targeting miR-181a-5p/FHDC

10.21203/rs.3.rs-389237/v1 ◽

2021 ◽

Author(s):

Suli Wang ◽

yingchun Wang ◽

Jinhua Wang ◽

Jin Lu ◽

Ke Li

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Inhibitory Effect ◽

Cell Counting ◽

Luciferase Reporter ◽

Ovarian Cancer Cell Lines ◽

Vital Effect ◽

And Migration

Abstract Previous reports indicate that LINC00665, a lincRNA, which is a naturally occurring long intergenic non-coding RNA exerts vital effect in a variety of cancers. Herein, we explore the role of LINC00665 in ovarian cancer. RT-qPCR was taken into the experiment to determine the expression level of LINC00665. Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, transwell, and EdU are employed to evaluate the effect of LINC00665 on cell proliferation, apoptosis, and migration in SKOV-3 and OVCAR-3 cells. The axis of LINC00665 and its specific miRNA, the miRNA target gene is explored in dual-luciferase reporter assay. Firstly, we find that LINC00665 is upregulated in ovarian cancer cell lines. Furthermore, not only the cell viability and in SKOV-3 and OVCAR-3 was reduced by LINC00665 knockdown but also cell proliferation and migration were inhibited. Afterwards, the bioinformatics analysis suggested that LNC00665 specifically binds to miR-181a-5p. Then, several studies confirmed that LINC00665 downregulated the miR-181a-5p in SKOV-3 and OVCAR-3 cells. The knockdown of miR-181a-5p evidently reverses the inhibitory effect of sh-LINC00662. Besides, FH2 Domain Containing 1 (FHDC1) has been proved to deed as an effective target of miR-181a-5p. In conclusion, the knockdown of LINC00665 facilitates ovarian cancer via development by sponging miR-181a-5p and upregulating FHDC1 expression.

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miR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy

10.21203/rs.3.rs-861069/v1 ◽

2021 ◽

Author(s):

Yang Zhou ◽

Chunyan Wang ◽

Jinye Ding ◽

Yaoqi Sun ◽

Zhongping Cheng

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cisplatin Resistance ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Cell Counting ◽

Luciferase Reporter ◽

Ovarian Cancer Cell Lines

Abstract Background Accumulating evidences reveal that aberrant microRNAs (miRNAs) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. Emerging evidences have demonstrated that miR-133a participates in tumorigenesis of various cancers. However, whether miR-133a is associated with cisplatin resistance in ovarian cancer remains unclear. Objective To investigate the role of miR-133a in the development of cisplatin resistance in ovarian cancer. Methods MiR-133a expression in cisplatin-resistant ovarian cancer cell lines was assessed by reverse-transcription quantitative PCR (RT-qPCR). Cell counting kit-8 (CCK-8) assay was used to evaluate cell viability of tumor cells treated with cisplatin in the presence or absence of miR-133a. Luciferase reporter assay was used to analyze binding of miR-133a with 3’ untranslated regions (3’UTR) of YES proto-oncogene 1 (YES1). The YES1 expression level was analyzed using the dataset from the international cancer genome consortiu (ICGC) and assessed by RT-qPCR and western blotting in vitro. The roles and mechanisms of YES1 on cell functions were further probed via gain- and loss-of-function analysis. Results The expression of miR-133a was significantly decreased in cisplatin resistant ovarian cancer cell lines (A2780-DDP and SKOV3-DDP), and the overexpression of miR-133a mimic reduced cisplatin resistance in A2780-DDP and SKOV3-DDP cells and the treatment of miR-133a inhibitor increased cisplatin sensitive in normal A2780 and SKOV3 cells. MiR-133a binds 3’UTR of YES1 and down-regulates its expression. Bioinformatics analysis revealed that YES1 expression was upregulated in recurrent cisplatin resistance ovarian cancer tissue and in vitro experiments also verified its upregulating in cisplatin resistance cell lines. Furthermore, we discovered that miR-133a down-regulated the expression of YES1 and thus inhibited the cell autophagy to reduce cisplatin resistance. Yes1 knockdown significantly suppressed the cisplatin resistance of ovarian cancer cells through inhibiting autophagy in vitro. Xenograft tumor implantation further demonstrated that Yes1 overexpression promoted ovarian tumor development and cisplatin resistance. Conclusion Our results suggest that miR-133a/YES1 axis plays a critical role in cisplatin resistance in human ovarian cancer by regulating cell autophagy, which might serve as a promising therapeutic target for ovarian cancer chemotherapy treatment in the future.

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miR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy

Cancer Cell International ◽

10.1186/s12935-021-02412-x ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Yang Zhou ◽

Chunyan Wang ◽

Jinye Ding ◽

Yingying Chen ◽

Yaoqi Sun ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cisplatin Resistance ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Cell Counting ◽

Luciferase Reporter ◽

Ovarian Cancer Cell Lines

Abstract Background Accumulating evidence has revealed that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. Emerging evidence has demonstrated that miR-133a participates in the tumorigenesis of various cancers. However, whether miR-133a is associated with cisplatin resistance in ovarian cancer remains unclear. Objective To investigate the role of miR-133a in the development of cisplatin resistance in ovarian cancer. Methods MiR-133a expression in cisplatin-resistant ovarian cancer cell lines was assessed by reverse-transcription quantitative PCR (RT–qPCR). A cell counting kit-8 (CCK-8) assay was used to evaluate the viability of tumour cells treated with cisplatin in the presence or absence of miR-133a. A luciferase reporter assay was used to analyse the binding of miR-133a with the 3′ untranslated region (3′UTR) of YES proto-oncogene 1 (YES1). The YES1 expression level was analysed using a dataset from the International Cancer Genome Consortium (ICGC) and assessed by RT–qPCR and western blotting in vitro. The roles and mechanisms of YES1 in cell functions were further probed via gain- and loss-of-function analysis. Results The expression of miR-133a was significantly decreased in cisplatin-resistant ovarian cancer cell lines (A2780-DDP and SKOV3-DDP), and the overexpression of the miR-133a mimic reduced cisplatin resistance in A2780-DDP and SKOV3-DDP cells. Treatment with the miR-133a inhibitor increased cisplatin sensitivity in normal A2780 and SKOV3 cells. MiR-133a binds the 3’UTR of YES1 and downregulates its expression. Bioinformatics analysis revealed that YES1 expression was upregulated in recurrent cisplatin-resistant ovarian cancer tissue, and in vitro experiments also verified its upregulation in cisplatin-resistant cell lines. Furthermore, we discovered that miR-133a downregulated the expression of YES1 and thus inhibited cell autophagy to reduce cisplatin resistance. Yes1 knockdown significantly suppressed the cisplatin resistance of ovarian cancer cells by inhibiting autophagy in vitro. Xenograft tumour implantation further demonstrated that Yes1 overexpression promoted ovarian tumour development and cisplatin resistance. Conclusions Our results suggest that the miR-133a/YES1 axis plays a critical role in cisplatin resistance in human ovarian cancer by regulating cell autophagy, which might serve as a promising therapeutic target for ovarian cancer chemotherapy treatment in the future.

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Sevoflurane and Desflurane Exposure Enhanced Cell Proliferation and Migration in Ovarian Cancer Cells via miR-210 and miR-138 Downregulation

International Journal of Molecular Sciences ◽

10.3390/ijms22041826 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1826 ◽

Cited By ~ 1

Author(s):

Masashi Ishikawa ◽

Masae Iwasaki ◽

Hailin Zhao ◽

Junichi Saito ◽

Cong Hu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cell Counting ◽

Immunofluorescent Staining ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.

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