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.

Prognostic Roles of LncRNA XIST and Its Potential Mechanisms in Human Cancers: A Pan-Cancer Analysis

“…But its mechanisms for pathogenesis are more than that. Recent studies have demonstrated that loss of XIST promotes tumor growth and invasion of BRCA due to the reduction of endogenous competition against onco-miRNAs [16,32]. However, its functions on tumors were not consistent in previous studies.…”

XIST sponges miR-320d to promote chordoma progression by regulating ARF6

“…By contrast, downregulation of XIST was observed in ovarian cancer cells and tissues, and XIST suppressed ovarian cancer cell proliferation and inversely promoted cell apoptosis [27] . Further, XIST overexpression hampered breast cancer cell progression in vitro and in vivo [28] . These results indicated that XIST played a different role in different cancers.…”

Long noncoding RNA ZBED3‐AS1 restrains breast cancer progression by targeting the microRNA‐513a‐5p/KLF6 axis

“…For instances, lncRNA LINC00899 alleviates malignant tumor behavior in BC through downregulating miR‐425 35 . LncRNA XIST upregulation exerts anti‐proliferation and pro‐apoptosis effects in BC cells by inhibiting miR‐326‐5p 36 . Importantly, lncRNA ADAMTS9‐AS1 overexpression inhibits miR‐513a‐5p to attenuate the aggressive traits of BC cells 18 .…”

“… 35 LncRNA XIST upregulation exerts anti‐proliferation and pro‐apoptosis effects in BC cells by inhibiting miR‐326‐5p. 36 Importantly, lncRNA ADAMTS9‐AS1 overexpression inhibits miR‐513a‐5p to attenuate the aggressive traits of BC cells. 18 In the present study, we revealed that ZBED3‐AS1 is a target of miR‐513a‐5p and is negatively related to miR‐513a‐5p expression, suggesting that ZBED3‐AS1 may be involved in BC by restraining miR‐513a‐5p.…”