Tags

Type your tag names separated by a space and hit enter

Downregulated lncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p.

Abstract

OBJECTIVE

The aim of this study was to elucidate the regulatory effect of long non-coding RNA (lncRNA) ADAMTS9-AS2 on Tamoxifen (TAM) resistance in breast cancer (BC), and to explore its underlying mechanism.

PATIENTS AND METHODS

TAM-resistant BC cell lines were first verified. Subsequently, cell proliferation and apoptosis were detected using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry, respectively. Protein levels of ABCB1, ABCC1, and ABCG2 in TAM-treated MCF-7 and MCF-7R cells were determined by Western blot. ADAMTS9-AS2 expression in BC tissues, para-cancerous tissues, as well as MCF-7 and MCF-7R cells, was accessed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between ADAMTS9-AS2 expression with pathological grade and tumor size of BC was explored. Chromatin fractionation was conducted to elucidate the subcellular distribution of ADAMTS9-AS2. The binding condition between ADAMTS9-AS2 and microRNA-130a-5p, as well as microRNA-130a-5p and PTEN, was verified by the dual-luciferase reporter gene assay. Furthermore, regulatory effects of ADAMTS9-AS2, microRNA-130a-5p, and PTEN on the proliferation and apoptosis of MCF-7R cells were determined.

RESULTS

MCF-7R cells were identified with TAM resistance. ADAMTS9-AS2 was lowly expressed in BC tissues and MCF-7R cells. Particularly, ADAMTS9-AS2 expression in BC tissues with grade III-IV or tumor size ≥2 cm was significantly lower than that of controls. Dual-luciferase reporter gene assay confirmed the binding condition between ADAMTS9-AS2 and microRNA-130a-5p, showing a negative correlation indicated by Pearson correlation analysis. PTEN was positively correlated with ADAMTS9-AS2. Overexpression of ADAMTS9-AS2 reversed the increased viability and decreased apoptosis induced by microRNA-130a-5p mimics transfection. In addition, PTEN knockdown reversed the decreased viability and accelerated apoptosis caused by ADAMTS9-AS2 overexpression.

CONCLUSIONS

We found that ADAMTS9-AS2 is lowly expressed in BC tissues and drug-resistant BC cells. Low expression of ADAMTS9-AS2 inhibits PTEN expression and enhances tamoxifen resistance through targeting microRNA-130a-5p.

Links

  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Center of Diagnosis and Treatment of Breast Disease, Qingdao University, Qingdao, China. hbwang66@126.com.

    ,

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30840279

    Citation

    Shi, Y-F, et al. "Downregulated lncRNA ADAMTS9-AS2 in Breast Cancer Enhances Tamoxifen Resistance By Activating MicroRNA-130a-5p." European Review for Medical and Pharmacological Sciences, vol. 23, no. 4, 2019, pp. 1563-1573.
    Shi YF, Lu H, Wang HB. Downregulated lncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p. Eur Rev Med Pharmacol Sci. 2019;23(4):1563-1573.
    Shi, Y. F., Lu, H., & Wang, H. B. (2019). Downregulated lncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p. European Review for Medical and Pharmacological Sciences, 23(4), pp. 1563-1573. doi:10.26355/eurrev_201902_17115.
    Shi YF, Lu H, Wang HB. Downregulated lncRNA ADAMTS9-AS2 in Breast Cancer Enhances Tamoxifen Resistance By Activating MicroRNA-130a-5p. Eur Rev Med Pharmacol Sci. 2019;23(4):1563-1573. PubMed PMID: 30840279.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Downregulated lncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p. AU - Shi,Y-F, AU - Lu,H, AU - Wang,H-B, PY - 2019/3/7/entrez SP - 1563 EP - 1573 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 23 IS - 4 N2 - OBJECTIVE: The aim of this study was to elucidate the regulatory effect of long non-coding RNA (lncRNA) ADAMTS9-AS2 on Tamoxifen (TAM) resistance in breast cancer (BC), and to explore its underlying mechanism. PATIENTS AND METHODS: TAM-resistant BC cell lines were first verified. Subsequently, cell proliferation and apoptosis were detected using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry, respectively. Protein levels of ABCB1, ABCC1, and ABCG2 in TAM-treated MCF-7 and MCF-7R cells were determined by Western blot. ADAMTS9-AS2 expression in BC tissues, para-cancerous tissues, as well as MCF-7 and MCF-7R cells, was accessed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between ADAMTS9-AS2 expression with pathological grade and tumor size of BC was explored. Chromatin fractionation was conducted to elucidate the subcellular distribution of ADAMTS9-AS2. The binding condition between ADAMTS9-AS2 and microRNA-130a-5p, as well as microRNA-130a-5p and PTEN, was verified by the dual-luciferase reporter gene assay. Furthermore, regulatory effects of ADAMTS9-AS2, microRNA-130a-5p, and PTEN on the proliferation and apoptosis of MCF-7R cells were determined. RESULTS: MCF-7R cells were identified with TAM resistance. ADAMTS9-AS2 was lowly expressed in BC tissues and MCF-7R cells. Particularly, ADAMTS9-AS2 expression in BC tissues with grade III-IV or tumor size ≥2 cm was significantly lower than that of controls. Dual-luciferase reporter gene assay confirmed the binding condition between ADAMTS9-AS2 and microRNA-130a-5p, showing a negative correlation indicated by Pearson correlation analysis. PTEN was positively correlated with ADAMTS9-AS2. Overexpression of ADAMTS9-AS2 reversed the increased viability and decreased apoptosis induced by microRNA-130a-5p mimics transfection. In addition, PTEN knockdown reversed the decreased viability and accelerated apoptosis caused by ADAMTS9-AS2 overexpression. CONCLUSIONS: We found that ADAMTS9-AS2 is lowly expressed in BC tissues and drug-resistant BC cells. Low expression of ADAMTS9-AS2 inhibits PTEN expression and enhances tamoxifen resistance through targeting microRNA-130a-5p. SN - 2284-0729 UR - https://www.unboundmedicine.com/medline/citation/30840279/Downregulated_lncRNA_ADAMTS9_AS2_in_breast_cancer_enhances_tamoxifen_resistance_by_activating_microRNA_130a_5p_ L2 - https://www.europeanreview.org/article/17115 DB - PRIME DP - Unbound Medicine ER -