LncRNA SNHG1 promotes tumor progression and cisplatin resistance through epigenetically silencing miR-381 in breast cancer

Abstract

The long-non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) is a known cause of tumorigenesis. Nevertheless, it’s yet unclear how lncRNA SNHG1 influences breast cancer. Herein, we explored the mechanisms through which SNHG1 modulates breast cancer tumor progression. Our findings demonstrated that SNHG1 is significantly upregulated in breast cancer tissues and cells. High SNHG1 levels were closely linked to reduced survival rates in breast cancer patients. SNHG1 silencing has been shown to inhibit the proliferative, migratory, and invasive activity of breast cancer cells. Moreover, SNHG1 silencing enhanced cisplatin (DDP) sensitivity of these cells through improving DDP-induced cell apoptosis. Mechanistically, SNHG1 was found to interact with enhancer of zeste homolog 2 (EZH2), recruiting EZH2 to trigger trimethylation of histone H3 lysine 27 (H3K27me3), thus epigenetically inhibiting miR-381 transcription in these cells. Overexpression of miR-381 inhibited tumor progression and sensitized cells to the chemotherapeutic reagent DDP. More importantly, rescue experiments demonstrated that miR-381 inhibition could inverse the tumor-suppressive effect of SNHG1 silencing in breast cancer. In summary, SNHG1 silencing suppressed tumor progression and overcame breast cancer cell DDP resistance via the epigenetic suppression of miR-381 expression. Our study revealed that SNHG1 served as a novel therapeutic target for breast cancer chemoresistance.

A high level of the long non-coding RNA MCF2L-AS1 is associated with poor prognosis in breast cancer and MCF2L-AS1 activates YAP transcriptional activity to enhance breast cancer proliferation and metastasis

“…Dysregulation of lncRNA expression patterns is now recognized as a prevalent finding in a variety of malignancies, with these ncRNAs having the ability to control oncogenic processes such as tumor cell motility, proliferation, survival, invasion, stemness, microenvironmental remodeling, and metastasis [ 42–44 ]. Several studies have examined the functions of lncRNAs in BC [ 9 , 10 , 31 ]. MCF2L-AS1 is a lncRNA that was recently identified and found to be dysregulated in multiple human cancer types in which it regulates progression-related disease processes [ 11 ].…”

“…The BT-549 and MDA-MB-231 BC cell lines were obtained from the American Type Culture Collection (VA, USA), while control MCF-10A cells were received from the Shanghai Institutes for Biological Sciences of the Chinese Academy of Sciences (Shanghai, China). The cell lines were cultured as previously described [ 10 ]. BC cell lines were cultured in high-glucose DMEM (Gibco, NY, USA) supplemented with 10% FBS (Biological Industries, Kibbutz Beit Haemek, Israel) as per recommended protocols, whereas MCF-10A cells were grown in F12/DMEM (Gibco) supplemented with 10% FBS.…”

Homeodomain-containing gene 10 contributed to breast cancer malignant behaviors by activating Interleukin-6/Janus kinase 2/Signal transducer and activator of transcription 3 pathway

“…To determine cell invasion ability, transwell chambers (EMD Millipore) were coated with Matrigel (BD, USA) [ 15 ]. BC cells were seeded in serum-free DMEM in the upper chamber.…”

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

“…The epigenetic silencing of miRNAs has been reported in various cancers [ 132 , 133 ] and played critical roles in anti-cancer drug resistance [ 134 ]. The role of DNMT1 in chemotherapy resistance has been reported [ 135 , 136 ].…”