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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Metastasis | Research

The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis

Authors: Xinjing Wang, Xiaoduan Li, Feikai Lin, Huizhen Sun, Yingying Lin, Ziliang Wang, Xipeng Wang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Ovarian cancer is highly lethal and has a poor prognosis due to metastasis. Long non-coding RNAs (lncRNAs) are key regulators of tumor development, but their role in ovarian cancer metastasis remains unclear.

Methods

The expression of lnc-CTSLP8 in ovarian cancer was analyzed in public databases (TCGA and GEO) and validated via qRT-PCR. Lnc-CTSLP8 overexpression and knockout cell lines were constructed using a lentiviral vector and the CRISP/Cas9 system. Cell proliferation, colony formation, migration, and invasion were analyzed. An ovarian orthotopic tumor mouse model was used for the in vivo study. Changes in autophagosomes, autolysosomes, and mitochondria in ovarian cancer cells were observed via transmission electron microscopy. EMT markers were detected by immunoblotting and immunofluorescence assays. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assays were performed to confirm the interaction between lnc-CTSLP8 and miR-199a-5p.

Results

A novel pseudogene, lnc-CTSLP8, was identified in ovarian cancer, with significantly elevated expression in metastatic tumor tissues compared to primary ovarian tumors. When overexpressed, lnc-CTSLP8 promoted ovarian cancer in vitro and in vivo by acting as a sponge for miR-199a-5p. Autophagy and EMT in ovarian cancer were also enhanced by lnc-CTSLP8. Mechanistically, lnc-CTSLP8 upregulated CTSL1 as a competitive endogenous RNA and exhibited oncogenic effects. Moreover, CTSL1 inhibitor treatment and miR-199a-5p overexpression abrogated the effects of lnc-CTSLP8 overexpression.

Conclusions

lnc-CTSLP8 acts as a ceRNA in ovarian cancer and represents a potential therapeutic target for metastatic ovarian cancer.

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Title: The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis
Authors: Xinjing Wang
Xiaoduan Li
Feikai Lin
Huizhen Sun
Yingying Lin
Ziliang Wang
Xipeng Wang
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Metastasis
Ovarian Cancer
Ovarian Cancer
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01957-z

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Abstract

Background

Methods

Results

Conclusions

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