Long-chain non-coding RNA GACAT1 promotes development and progression of breast cancer by targeting microRNA-875-3p

Abstract

Role of long-chain non-coding ribonucleic acid (lncRNA) GACAT1 in the development of breast cancer and its possible mechanism were investigated. The levels of GACAT1, microRNA-875-3p and Stonin2 (STON2) in breast cancer tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The level of GACAT1 in breast cancer cell lines was further explored. The effects of GACAT1 and microRNA-875-3p on cell proliferation and cycle were detected by cell counting kit-8 (CCK-8) and flow cytometry. The binding relationship between microRNA-875-3p and STON2, microRNA-875-3p and GACAT1 was examined by a dual luciferase reporting assay. It was confirmed by rescue experiments whether GACAT1 canregulate the level of STON2 by binding to microRNA-875-3p. GACAT1 level was clearly enhanced in breast cancer tissues compared to that of the adjacent tissues. Similar result was observed in breast cancer cell lines. Upregulation of GACAT1 promoted the proliferation and cycle of breast cancer cells including MCF-7 and BCap-37. The dual luciferase reporting assay results indicated that GACAT1 had a binding relationship with microRNA-875-3p. Further experiments confirmed that microRNA-875-3p was conspicuously downregulated in breast cancer tissues, and upregulation of microRNA-875-3p could inhibit the proliferation ability of MCF-7 and BCap-37 cells, and partially reversed the promoting effect of GACAT1 on cell cycle. Through bioinformatics prediction and dual luciferase reporter gene experiments, we found that STON2 might be a target gene of microRNA-875-3p. Overexpression of STON2 could partially abolish the effect of microRNA-875-3p on cell proliferation and cycle of MCF-7 and BCap-37 cells. GACAT1 can participate in the progression of breast cancer by promoting the proliferation and cycle of breast cancer cells. The mechanism may be through the regulation of the level of STON2 by adsorbing microRNA-875-3p.

Downregulation of long non‑coding RNA GACAT1 suppresses proliferation and induces apoptosis of NSCLC cells by sponging microRNA‑422a

“…GAcAT1 expression was found to be increased in gastric cancer and promoted cancer cell proliferation, invasion, and migration (22). Similarly, overexpressed GAcAT1 drove breast cancer development by facilitating proliferation and cell cycle progression (23). In the present study, GAcAT1 knockdown inhibited proliferation, induced apoptosis, and the cell cycle arrest of NScLc cells, supporting its oncogenic role in different types of cancer.…”

“…Research into the ceRNA regulatory network suggested that lncRNAs act as endogenous decoys for miRNAs, which in turn affected the binding of miRNAs to the mRNA targets. GACAT1 was found to target miR-875-3p and regulated breast cancer progression ( 23 ). A recent study reported that GACAT1 modulated ZBTB2 and SP1 mRNA expression levels by sponging miR-149 in gastric cancer ( 22 ).…”

“…Decreased GACAT1 expression was identified in gastric cancer and was significantly associated with lymph node metastasis, differentiation, and TNM stages in patients with gastric cancer ( 20 - 22 ). GACAT1 was also reported to promote breast cancer development and progression ( 23 ). These findings revealed an important function of GACAT1 in tumorigenesis; however, the functional roles and associated mechanism of GACAT1 in NSCLC have rarely been reported.…”

LncRNA GACAT1 induces tongue squamous cell carcinoma migration and proliferation via miR‐149

“…Recently, Zhong et al 34 showed that GACAT1 was decreased in NSCLC tissues, and knockdown of GACAT1 inhibited cell growth and promoted apoptosis via suppressing miR‐422a. Wang et al 35 indicated that GACAT1 induced breast tumour progression via sponging miR‐875‐3p. However, its role and mechanism in TSCC development have not been studied.…”

LncRNA GACAT1 targeting miRNA-149 regulates the molecular mechanism of proliferation, apoptosis and autophagy of oral squamous cell carcinoma cells

“…For example, lncRNA MIAT can bind miR-1301-3p through “sponge” effect, and then form lncRNA MIAT/miR-1301-3p/INCENP regulatory pathway with the target gene INCENP of miR-1301-3p, which affects the progress of esophageal squamous cell carcinoma [ 9 ]. A large number of evidences indicate that lncRNA GACAT1 is involved in the occurrence and development of tumors [ 10 – 12 ]. It is overexpressed in many tumor cells, and inhibition of lncRNA GACAT1 expression can not only terminate cell transformation, but also reverse cell malignant transformation.…”