LncRNA SNHG10 suppresses the development of doxorubicin resistance by downregulating miR-302b in triple-negative breast cancer
Aini Shataer, Shayiti Bolati, Wei Ding, Siyin Liu, Pengcheng Su, Saiding Aili, Yimin Naman, Xuekelaiti Kuerban
Abstract
Unlike other types of breast cancer, triple negative breast cancer (TNBC) does not respond to therapies targeting human epidermal growth factor receptor-2 (HER2) or hormone therapy, and the prognosis of patients with TNBC is usually poor. The role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 10 (SNHG10) has been investigated in many types of cancer, but its role in TNBC is unknown. This study aimed to explore the role of SNHG10 in TNBC in the context of doxorubicin treatment, a common therapy for TNBC. Analysis of the TCGA dataset revealed the downregulation of SNHG10 in TNBC. The downregulation of SNHG10 of TNBC in TNBC was further confirmed by detecting its expression in 60 patients with TNBC by qPCR. The expression of SNHG10 was further downregulated after doxorubicin treatment. In TNBC, microRNA-302b (miR-302b) was downregulated and was positively correlated with SNHG10. In TNBC cells, overexpression of SNHG10 resulted in upregulation of miR-302b, and methylation-specific PCR analysis showed that SNHG10 negatively regulates the methylation of miR-302b. In addition, doxorubicin treatment resulted in the downregulation of SNHG10 in TNBC cells, and overexpression of SNHG10 and miR-302b promoted apoptosis of doxorubicin-treated TNBC cells. Furthermore, overexpression of both SNHG10 and miR-302b had a stronger effect on apoptosis than that of overexpression of SNHG10 alone. Our study showed that SNHG10 could inhibit the development of resistance to doxorubicin by upregulating miR-302b in TNBC through methylation. Our findings suggested that SNHG10 might serve as a molecular target for intervening in TBNC metastasis.