lncRNA CYTOR promotes tamoxifen resistance in�breast cancer cells via sponging miR‑125a‑5p

Abstract

development of resistance to endocrine therapy, such as tamoxifen, remains a tricky clinical problem during the treatment of breast cancer. Accumulating evidence suggested that dysregulation of long noncoding (lnc_RNAs contributes to the development of tamoxifen resistance. In the current study, via screening, cytoskeleton regulator RNA (cYTOR) was identified as the most significantly elevated lncRNA in the established tamoxifen resistant McF7 cell lines (McF7/TAM1 and McF7/TAM2) compared with the parental McF7 cells (McF7-P). The ccK-8 assay indicated that silencing of cYTOR increased the sensitivity of McF7/TAM1 and McF7/TAM2 to tamoxifen treatment. Using bioinformatic analysis, it was predicted that microRNA (miR)-125a-5p might bind to cYTOR and the expression of miR-125a-5p was negatively correlated with cYTOR in the tumor tissues of breast cancer. In addition, RT-qPcR and dual luciferase assays validated that cYTOR directly repressed miR-125a-5p expression in breast cancer cells. Through regulation of miR-125a-5p, cYTOR elevated serum response factor (SRF) expression and activated Hippo and mitogen associated protein kinase signaling pathways to promote breast cancer cell survival upon tamoxifen treatment. In the collected tumor tissues of breast cancer in the present study, high expression of cYTOR was detected in tissues from patients with no response to tamoxifen compared with those from patients who were not treated with tamoxifen. A positive correlation between cYTOR and SRF mRNA expression was observed in tissues collected from patients with breast cancer. In conclusion, the results of the present study demonstrated a pivotal role of cYTOR in mediating tamoxifen resistance in breast cancer.

The crosstalk between lncRNAs and the Hippo signalling pathway in cancer progression

“…Mechanistically, YAP and Runx2 together displayed an oncogenic activity by hindering lncRNA MT1DP in a FoxA1‐dependent manner in liver cancer 47 . Other lncRNAs that are regulated by Hippo signalling pathway include cytoskeleton regulator RNA (CYTOR), 50,51 non‐coding RNA activated by DNA damage (NORAD) 52 and H19 53 . LncRNA CYTOR, also known as long intergenic ncRNA 00 152 (LINC00152), is located on chromosome 2p11.2 with a length of 828 nucleotides 54 .…”

LncRNA CYTOR Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a CeRNA for miR-10a-5p

“…CYTOR has been characterized as an oncogenic lncRNA in many types of cancers [15,16]. In cancers, CYTOR is overexpressed to promote cancer development by increasing cell proliferation and suppressing cell apoptosis [15,16].…”

“…However, in vivo animal model experiments and clinical trials are needed to test our hypothesis. It is also worth noting that CYTOR suppress cell apoptosis in both cancers [15,16] and OA. Therefore, CYTOR may play similar roles in cell apoptosis in different human diseases.…”

<p>Long Non-Coding RNAs in Drug Resistance of Breast Cancer</p>

“…LncRNA CYTOR promotes TAM resistance by increasing serum response factor (SRF) and activating the MAPK signaling pathway by sponging miR-125a-5p in MCF-7/TAM cells. 81 Sun et al identified a novel AIs / / / / / Notes: "↑" represents upregulation; "↓" represents downregulation; "/" represents not mentioned.…”

“…68 TINCR sponges miR-125b and promotes TZB resistance in HER-2+ BC cells. 100 Other lncRNAs such as FTH1P3, 67 LINC00511, 69 ATB, 103 CYTOR, 81 DSCAM-AS1, 83,84 ROR, 86 ADAMTS9-AS2, 91 LINC00894-002, 92 NONHSAT101069, 29 and PRLB 77 sponge specific miRNAs to regulate drug resistance in BC.…”