miR‐155 increases stemness and decitabine resistance in triple‐negative breast cancer cells by inhibiting TSPAN5

Abstract

Effective therapeutic targets for triple‐negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration‐approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR‐155 is upregulated in BC, but whether and how miR‐155 regulates DCA resistance is unclear. In this study, we demonstrated that miR‐155 was upregulated in CD24−CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR‐155 increased the number of CD24−CD44+ CSCs, DCA resistance and tumor clone formation in MDA‐231 and BT‐549 BC cells, and knockdown of miR‐155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR‐155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin‐5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR‐155 in promoting stemness and DCA resistance in BC cells. Our data show that miR‐155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR‐155/TSPAN5 signaling axis in the treatment of TNBC.

Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy

“…Neoadjuvant chemotherapy (NAC) remains the gold standard form of therapy for TNBC patients, with limited effectiveness, narrower durations of response, and considerably toxic profiles 2 . As a highly heterogeneous BC subtype, there are very few options for treating TNBC patients that confer resistance to conventional chemotherapy 3 . Not only does TNBC lack targeted therapy options, but it is also the most aggressive subtype with higher incidences of metastasis, early recurrence and poor overall survival, accounting for around 15-20% of all BC cases [4][5][6] .…”

lncRNA CASC2 Enhances 131I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155

“…In order to better understand that ceRNA mechanism allows CASC2 in 131 I sensitivity, the target of miR-155 might be helpful. We used DIANA tools to predict 10 targets of miR-155, which were reported to be relevant to radioresistance [ 21 , 26 – 34 ]. As one of the predicted targets, forkhead box O3 (FOXO3) was involved in miR-155-mediated regulation of radio- or chemoresistance in thyrocytes [ 35 , 36 ].…”

The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

“…There-after, pre-miRNAs move into the cytoplasm via exportin 5, with stem-loop structures, and are processed into mature miRNAs by Drosha, Dicer (RNase III), RNA polymerase III, and other related molecules [58]. These mature miRNAs then bind the RNA-induced silencing complex (RISC), and the resulting co-complex directly binds the 3 -untranslated regions (3 -UTRs) of target mRNAs, acting as a suppressor of translation or helping to increase degradation [59]. Thus, dependent upon the target mRNAs' identity, miRNAs control various physiological functions, including cell growth, proliferation, differentiation, development, reproduction, apoptosis, metabolism, and its abnormal expression in various cancers, including TNBC [60].…”