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LncRNA FGD5-AS1 promotes the malignant phenotypes of ovarian cancer cells via targeting miR-142-5p

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Abstract

Long non-coding RNAs (lncRNAs) have been reported to participate in regulating gene expression and are related to tumor progression. FGD5 antisense RNA 1 (FGD5-AS1) facilitates the progression of various tumors. However, the expression and function of FGD5-AS1 in ovarian cancer (OC) and its mechanism of action are not yet clear. Real-time polymerase chain reaction (RT-PCR) was employed to explore the expression levels of FGD5-AS1 and miR-142-5p in OC. The relationship between the expression of FGD5-AS1 and clinicopathological indicators of OC patients was analyzed by χ2 test. CCK-8 assay, BrdU assay, and Transwell assay were carried out to detect cell proliferation, migration, as well as invasion, respectively. Subcutaneous tumorigenesis experiment and lung metastasis model were used to examine the biological effects of FGD5-AS1 in OC in vivo. Dual luciferase reporter gene assay or RIP experiment was employed to explore the targeting relationship between FGD5-AS1 and miR-142-5p, as well as miR-142-5p and PD-L1 3′UTR. First, we found that FGD5-AS1 was markedly up-regulated in OC. Moreover, its high expression level was associated with positive local lymph node metastasis and higher T stage in OC patients. Gain-of-function and loss-of-function assays demonstrated that FGD5-AS1 facilitated the proliferation, migration, as well as invasion of OC cells. Mechanistically, it was revealed that FGD5-AS1 targeted miR-142-5p to repress its expression and function. Furthermore, miR-142-5p has a binding site for 3’ UTR of PD-L1, and FGD5-AS1 could positively regulate PD-L1 expression via repressing miR-142-5p. The present study reports that FGD5-AS1/miR-142-5p/PD-L1 axis is involved in regulating OC progression.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

We thank Hubei Yican Health Industry Co., Ltd. (Wuhan, China) for its linguistic assistance during the preparation and revision of this manuscript.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Third Hospital of Jilin University, 126th Xiantai Street, Changchun, 130021, Jilin, China

    Zhang Aichen, Wang Kun, Sun Xiaochun & Tong Lingling

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  1. Zhang Aichen
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  2. Wang Kun
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  3. Sun Xiaochun
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Contributions

Conceived and designed the experiments: ZAC, SXC, TLL; Performed the experiments: ZAC, WK, SXC, TLL; Statistical analysis: SXC, TLL; Wrote the paper: ZAC, SXC, TLL. All authors read and approved the final manuscript.

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Correspondence to Sun Xiaochun or Tong Lingling.

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The authors declare that they have no competing interests.

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Our study was approved by the Ethics Review Board of China-Japan Union Hospital of Jilin University.

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Supplementary Information

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10495_2021_1674_MOESM1_ESM.tif

Supplementary figure 1 The role of FGD5-AS1 on IOSE cell. (A) FGD5-AS1 overexpressed plasmid and si-FGD5-AS1 were transfected into IOSE cells respectively, and the transfection was verified by RT-PCR. (B) CCK-8 experiment were employed to examine the proliferation of OC cells. * symbolizes P < 0.05. Supplementary file1 (TIF 207 kb)

10495_2021_1674_MOESM2_ESM.tif

Supplementary figure 2 The KEGG pathways that are enriched for the miR-142-5p targets are mainly cancer-specific pathways. Supplementary file2 (TIF 445 kb)

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Aichen, Z., Kun, W., Xiaochun, S. et al. LncRNA FGD5-AS1 promotes the malignant phenotypes of ovarian cancer cells via targeting miR-142-5p. Apoptosis 26, 348–360 (2021). https://doi.org/10.1007/s10495-021-01674-0

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