J Breast Cancer.  2020 Aug;23(4):343-354. Triple negative breast neoplasms.

LncRNA DLG1-AS1 Promotes Cancer Cell Proliferation in Triple Negative Breast Cancer by Downregulating miR-203

• Li S

• KMID: 2511795
• DOI: http://doi.org/Triple negative breast neoplasms

Abstract

Purpose
The oncogenic role of long non-coding RNA (lncRNA) DLG1-AS1 has been studied in cervical cancer, but its involvement in triple negative breast cancer (TNBC) is unknown. Here, we aimed to investigate the possible role and underlying mechanism of DLG1-AS1 in TNBC.
Methods
The differential expression of DLG1-AS1 and miR-203 in TNBC tissues and cells was determined using quantitative polymerase chain reaction assays. Correlations between DLG1-AS1 and miR-203 expression across TNBC tissues and non-tumor tissues were analyzed using Spearman rank correlation test. The effects of DLG1-AS1 and miR-203 overexpression, and DLG1-AS1 knockdown on the metastasis of BT-549 and MDA-MB-157 cells were evaluated using a transwell assay. The effects of DLG1-AS1 and miR-203 overexpression on the proliferation of BT-549 and MDA-MB-157 cells were evaluated using Cell Counting Kit-8 and cell colony formation assays.
Results
We found that DLG1-AS1 was upregulated whereas miR-203 was downregulated in tumor tissues of patients and in TNBC cells compared to the adjacent healthy tissues of patients with TNBC and in normal breast MCF-10A cells, respectively. Further, DLG1-AS1 and miR-203 were inversely correlated in tumor tissues. DLG1-AS1 overexpression mediated downregulation of miR-203, whereas miR-203 overexpression had no significant effects on DLG1-AS1 expression. DLG1-AS1 expression was increased, whereas miR-203 levels were decreased with advancing clinical stages. TNBC cell migration was promoted by DLG1-AS1 overexpression and inhibited by miR-203 overexpression or DLG1-AS1 knockdown. Moreover, TNBC cell proliferation was promoted by DLG1-AS1 overexpression and inhibited by miR-203 overexpression. Further, miR-203 overexpression reduced the effects of DLG1-AS1 overexpression.
Conclusion
These results indicate that DLG1-AS1 may promote cancer cell proliferation in TNBC by downregulating the tumor suppressor miR-203.

Keyword

Cell proliferation; Oncogene; RNA; long noncoding; Triple negative breast neoplasms