Long Noncoding RNA XIST Acts as a ceRNA of miR-362-5p to Suppress Breast Cancer Progression.

Abstract

Background: Long noncoding RNAs (lncRNAs) X inactivate-specific transcripts (XIST) have been found to be dysregulated in breast cancer (BC). Nevertheless, the influence and mechanism of XIST on BC progression remain largely undefined. Methods: The expression levels of XIST, miR-362-5p, and ubiquitin-associated protein 1 (UBAP1) mRNA were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion abilities were determined using MTT assay, flow cytometry, and transwell assay, respectively. Targeted relationship between miR-362-5p and XIST or UBAP1 was validated by the dual-luciferase reporter assay. Western blot was performed to evaluate UBAP1 protein level. Xenograft mice model was established for the investigation of XIST in tumor growth. Results: The authors' data indicated that XIST and UBAP1 were downregulated in BC tissues and cells. XIST overexpression weakened BC cell proliferation, migration, invasion, and facilitated the apoptosis, and XIST silencing exerted opposite effect. Mechanistically, XIST directly interacted with miR-362-5p and miR-362-5p mediated the regulatory effects of XIST overexpression on BC cell malignant behaviors. UBAP1 was a direct target of miR-362-5p. MiR-362-5p exerted its regulatory effects on BC cell behaviors by UBAP1. Moreover, XIST modulated UBAP1 expression through acting a competing endogenous RNA of miR-362-5p. XIST overexpression mediated antiproliferation, antimigration, anti-invasion, and proapoptosis effects were abated by the restored expression of UBAP1 in BC cells. Furthermore, the upregulation of XIST hindered tumor growth in vivo. Conclusion: The current study suggested that XIST overexpression hampered BC cell progression in vitro and in vivo at least partially by targeting the miR-362-5p/UBAP1 axis, illuminating XIST as a promising therapeutic agent for BC management.

• Authors: Baoyin Liu, Chengyu Luo, Hua Lin, Xiaoxin Ji, Enyu Zhang, Xin Li
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 36 Issue 6 Pg. 456-466 (Aug 2021) ISSN: 1557-8852 [Electronic] United States
• PMID: 32749857 (Publication Type: Journal Article)

Chemical References

• MIRN362 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• XIST non-coding RNA

Topics

• Animals
• Breast Neoplasms (genetics)
• Disease Progression
• Female
• Humans
• Mice
• MicroRNAs (metabolism)
• Middle Aged
• RNA, Long Noncoding (metabolism)