NEAT1/miR‑124/STAT3 feedback loop promotes breast cancer progression

Abstract

The long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) has important roles in the regulation of multiple cell functions, such as proliferation, apoptosis and migration. However, the mechanism by which NEAT1 regulates breast cancer progression is not well elucidated. In the present study, NEAT1 and microRNA-124 (miR-124) levels were detected by reverse transcription-quantitative PCR in breast cancer tissues and cell lines. STAT3 protein levels were detected by western blot analysis. Cell proliferation and cell cycle distribution were determined using MTT and colony formation assays, and flow cytometry, respectively. The results demonstrated that NEAT1 and STAT3 expression levels were increased in breast cancer tissues compared with normal breast tissues, whereas miR-124 expression was significantly decreased. Functional analyses revealed that NEAT1 promoted cell proliferation and cell cycle progression in breast cancer cells. Additionally, NEAT1 and STAT3 expression levels were negatively correlated with miR-124 levels in breast cancer tissues. A direct interaction between miR-124, and NEAT1 and STAT3, was predicted by bioinformatics analysis and confirmed using a luciferase activity assay. NEAT1 overexpression markedly increased STAT3 protein expression levels, and this effect was reversed by miR-124 overexpression in breast cancer cells. Furthermore, miR-124 overexpression partially attenuated the effects of NEAT1 on breast cancer cell proliferation and cell cycle progression. The inhibitory effects of miR-124 overexpression on the proliferation rate and cell cycle progression were abolished by STAT3 overexpression. In turn, STAT3 silencing inhibited NEAT1 transcription in breast cancer cells. In summary, the present findings revealed that NEAT1 and STAT3 formed a feedback loop via sponging miR-124 to promote breast cancer progression.

miR-124 and miR-203 synergistically inactivate EMT pathway via coregulation of ZEB2 in clear cell renal cell carcinoma (ccRCC)

“…Both miR-124 and miR-203 are known to be aberrantly expressed and play tumor suppressive roles in a wide range of human cancers. Deregulation of miR-124 has been demonstrated in liver cancer [16], breast cancer [17][18][19], colorectal cancer [20], lung carcinoma [21] and nasopharyngeal carcinoma [21]. miR-203 has also been shown to be deregulated in multiple types of tumor entities, e.g.…”

Role of STAT3 signaling pathway in breast cancer

“…Then, phosphorylated STAT3 forms a homodimer and translocates into the nucleus to bind to the promotor region of target genes and activates target gene transcription abundant transcript 1 (NEAT1) forms a feedback loop with STAT3 to promote breast cancer progression. However, NEAT1 is suppressed by miR-124 [20]. Interestingly, glucosamine is found to suppress the activation of STAT3 and decrease breast cancer stemness and progression [21].…”

MRPS30-DT Knockdown Inhibits Breast Cancer Progression by Targeting Jab1/Cops5

“…Meng et al used bioinformatics to show that four lncRNAs are highly expressed in breast cancer and were significantly positively correlated with OS and metastasis (27). Peng et al discovered that lncRNA NEAT1 is upregulated in breast cancer and promotes cancer progression via the NEAT1/miR-124/STAT3 axis (28). Increasing evidences have testified that lncRNAs can regulate the expression of their adjacent genes in cis or modulate gene transcription in trans through epigenetic, transcriptional, and posttranscriptional mechanisms (29).…”