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Long non-coding RNA LINC00858 aggravates the oncogenic phenotypes of ovarian cancer cells through miR-134-5p/RAD18 signaling

Archives of Gynecology and Obstetrics volume 302, pages 1243–1254 (2020)Cite this article

Abstract

Purpose

Ovarian cancer is a common gynecological cancer. Herein, we focused on the function and probable mechanisms of LINC00858 in ovarian cancer.

Methods

Real-time quantitative polymerase chain reaction (RT-qPCR) was employed for detecting the expression of LINC00858, miR-134-5p and RAD18 E3 ubiquitin protein ligase (RAD18). Cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and apoptosis were detected by cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), transwell, terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) and western bolt experiments, as appropriate. Interplays between LINC00858, miR-134-5p and RAD18 were detected by RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays.

Results

LINC00858 were up-regulated in ovarian cancer tissues and cells, and its expression was elevated in advanced samples compared to early ones. Knocking down LINC00858 inhibited cell proliferation, motility and EMT, but accelerated cell apoptosis in ovarian cancer. Moreover, could be sponged by LINC00858 sponged miR-134-5p to enhance RAD18 expression in ovarian cancer. Also, silenced RAD18 could also restrain oncogenic behaviors of ovarian cancer cells. Rescue experiments showed that overexpressing RAD18 reversed the effects caused by knocking down LINC00858 on cellular processes.

Conclusion

LINC00858 sequestered miR-134-5p to elevate RAD18 expression, resulting in aggravated development of ovarian cancer. This might provide promising targets for treating patients with ovarian cancer.

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Abbreviations

LINC00858:

Long intergenic non-protein coding RNA 858

RAD18:

RAD18 E3 ubiquitin protein ligase

ncRNAs:

Non-coding RNAs

lncRNAs:

Long non-coding RNAs

ceRNAs:

Competing endogenous RNAs

miRNAs:

MicroRNAs

mRNA:

Messenger RNA

ATCC:

American type culture collection

RPMI:

Roswell Park Memorial Institute

FBS:

Fetal bovine serum

RT-qPCR:

Real-time quantitative polymerase chain reaction

CCK-8:

Cell counting kit-8

EdU:

5-Ethynyl-2′-deoxyuridine

TdT:

Terminal deoxynucleotidyl transferase

TUNEL:

DUTP Nick-End Labeling

SDS-PAGE:

Sulphate–polyacrylamide gel electrophoresis

PVDF:

Polyvinylidene fluoride

HRP:

Horseradish peroxidase

FISH:

Fluorescence in situ hybridization

RIP:

RNA immunoprecipitation

WT:

Wild-type

Mut:

Mutant

SD:

Standard deviation

ANOVA:

Analysis of variance

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Acknowledgement

Our sincere gratitude goes to all the experimenters.

Funding

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Author information

Affiliations

  1. Department of Laboratory Medicine, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China

    Heng Xue, Zhihui Wu, Dongdong Rao & Bimin Zhuo

  2. Department of Laboratory Medicine, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, Fujian, China

    Qingquan Chen

Authors
  1. Heng Xue
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  2. Zhihui Wu
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  3. Dongdong Rao
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  4. Bimin Zhuo
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  5. Qingquan Chen
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Contributions

XH designed this study. XH, WZ and RD performed experiments and analyzed data. ZB was responsible for investigation and preparation. CQ contributed to manuscript. All authors read and approved final manuscript.

Corresponding author

Correspondence to Qingquan Chen.

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This work was supported by the approval of Ethics Committee of Fujian Maternity and Child Health Hospital. All the participants signed the informed consents before the study.

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404_2020_5722_MOESM1_ESM.tif

Figure S1 A. The expression of LINC00858 in 70 pairs of ovarian cancer samples was detected by RT-qPCR. B. LINC00858 level in 31 tumor tissues from ovarian cancer patients at stage stage I–II and 39 specimens from patients at stage III–IV was determined by RT-qPCR. **P < 0.01 (TIF 131 kb)

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Xue, H., Wu, Z., Rao, D. et al. Long non-coding RNA LINC00858 aggravates the oncogenic phenotypes of ovarian cancer cells through miR-134-5p/RAD18 signaling. Arch Gynecol Obstet 302, 1243–1254 (2020). https://doi.org/10.1007/s00404-020-05722-z

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  • DOI: https://doi.org/10.1007/s00404-020-05722-z

Keywords

  • LINC00858
  • miR-134-5p
  • RAD18
  • Ovarian cancer