LncRNA SNHG10 suppresses the development of doxorubicin resistance by downregulating miR-302b in triple-negative breast cancer

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.

The miR‐302/367 cluster: Aging, inflammation, and cancer

“…Adriamycin resistance is prevented from developing in triple-negative BC by upregulating the expression of miR-302b via methylation. 91 MiR-302b cannot considerably slow the growth of triple-negative BC on its own. MiR-302b affects various molecular processes, including DNA repair, cell cycle, and stemness, to improve the response to cisplatin.…”

“…It can also improve the sensitivity of triplenegative BC to cisplatin by controlling the E2F family-negative1 genome-wide transcriptome analysis and integrin subunit alpha 6 axis. 92 MiRNAs can control oncogenic pathways, which are crucial for the development of tumors; whether they are overexpressed or otherwise dysfunctional, 91 many studies have identified miR-302/ T A B L E 1 MiR-302/367 cluster is aberrantly expressed in different diseased tissues or cells, thus playing an important role in repressing target genes or participating in the regulatory axis. 93 Given that miR-302b-3p binds PTEN to activate the AKT pathway and that miR-302b-3p inhibition blocks PTEN/AKT pathway-related neuronal damage, it is possible that miR-302b-3p is a key target for ISOinduced neuronal injury.…”

“…In BCs that were triple‐negative, MiR‐302b expression was downregulated. Adriamycin resistance is prevented from developing in triple‐negative BC by upregulating the expression of miR‐302b via methylation 91 . MiR‐302b cannot considerably slow the growth of triple‐negative BC on its own.…”

“…MiRNAs can control oncogenic pathways, which are crucial for the development of tumors; whether they are overexpressed or otherwise dysfunctional, 91 many studies have identified miR‐302/367 cluster members that may act as oncogenes and tumor suppressors. MiR‐302/367 cluster functions in tumors deserve to be fully understood and may provide valuable therapeutic strategies for disease prevention, cure, and prognosis.…”

Insights into the involvement of long non-coding RNAs in doxorubicin resistance of cancer

“…LncRNA SNHG10 was downregulated in triple negative breast cancer (TNBC) cells after DOX treatment, and overexpression of SNHG10 significantly promoted DOX-induced apoptosis. Mechanism research showed that SNHG10 could inhibit the development of resistance to DOX by upregulating miR-302b through methylation modulation ( Aini et al, 2022 ).…”