The Long Noncoding RNA MEG3 Retains Epithelial-Mesenchymal Transition by Sponging miR-146b-5p to Regulate SLFN5 Expression in Breast Cancer Cells

Abstract

More and more studies have shown that long noncoding RNAs (lncRNAs) play essential roles in malignant tumors. The lncRNA MEG3 serves as a crucial molecule in breast cancer development, but the specific molecular mechanism needs to be further explored. We previously reported that Schlafen family member 5 (SLFN5) inhibits breast cancer malignant development by regulating epithelial-mesenchymal transition (EMT), invasion, and proliferation/apoptosis. Herein, we demonstrated that MEG3 was downregulated in pan-cancers and correlated with SLFN5 expression positively in breast cancer by bioinformatics analysis of TCGA and UCSC Xena data. Intervention with MEG3 positively affected SLFN5 expression in breast cancer cells. MEG3 repressed EMT and migration/invasion, similar to our previously reported functions of SLFN5 in breast cancer. Through bioinformatics analysis of starBase and LncBase data, 12 miRNAs were found to regulate both SLFN5 and MEG3, in which miR-146b-5p was confirmed to be regulated by MEG3 using MEG3 siRNA and overexpression method. MiR-146b-5p could bind to both SLFN5 3 ′ UTR and MEG3, and inhibit their expression in a competing endogenous RNA mechanism, assayed by luciferase reporter and RNA pull down methods. Therefore, we conclude that MEG3 positively modulates SLFN5 expression by sponging miR-146b-5p and inhibits breast cancer development.

Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1

“…It has been established that lncRNAs may function as oncogenes or tumour suppressors in the progression and metastasis of breast cancer and have great potential as diagnostic and prognostic biomarkers [22]. An increasing number of studies have revealed that MEG3 is downregulated and represses cell proliferation, migration, and invasion, and induces apoptosis in breast cancer cells [23][24][25][26][27]. The present study confirmed the downregulation of MEG3 in both tumour tissue and breast cancer cells, showing consistent effects on cell proliferation, migration, invasion, and apoptosis.…”

Progress in investigating the relationship between Schlafen5 genes and malignant tumors

“…Additionally, it maintains and restores the epithelial morphology of breast cancer cells by downregulating ZEB1 transcription, thereby preventing EMT in breast cancer. Li et al (35), through bioinformatics analysis of TCGA data, discovered that miR-146b-5p can bind to the SLFN5 3'UTR and MEG3, demonstrating that MEG3 positively regulates SLFN5 expression and inhibits breast cancer development through sequestration of miR-146b-5p (see Figure 1). MEG3 is downregulated in various cancers and positively correlates with SLFN5 expression in breast cancer (36, 37).…”