Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

Abstract

Background/Aims: An increasing body of evidence shows that long noncoding RNAs (lncRNAs) are involved in many different cancers. In this study, we aimed to investigate the competing endogenous RNA (ceRNA)-dependent mechanism by which the lncRNA GAS5 contributes to the development of breast cancer. Methods: A total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected. The human breast cancer cell lines MDA-MB-231, MDA-MB-453, BT549, SK-BR-3 and MCF-7 and human breast cell line MCF10A were utilized in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect expression of relative factors. RNA immunoprecipitation (RIP) was used to evaluate the relationship between GAS5 and miR-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between ATG3 and miR-23a. A subcutaneous xenograft nude mouse model was generated to examine the role of GAS5 and its regulatory pathway in autophagy. Results: GAS5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (TNM) stage and estrogen receptor-negative (ER-) breast cancer tissues. More importantly, we found that GAS5 promoted autophagy, with enhanced autophagosome formation after GAS5 overexpression. GAS5 was found to act as a microRNA sponge in a pathway that included miR-23a and its target gene ATG3. The GAS5-miR-23a-ATG3 axis significantly regulated autophagy in vivo and in vitro. Conclusions: In summary, we report that the GAS5-miR-23a-ATG3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.

MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis

“…LncRNAs have been well known to exert roles by acting as a competitive endogenous RNA (ceRNA) to segregate microRNAs (miRNAs) away from target mRNAs [15][16][17]. Using bioformatics analysis, we noted that KLF3-AS1 harbors putative binding sites of miR-206.…”

“…Furthermore, GIT1 was identified as a putative target of miR-206 by harboring a miR-206 binding sequence in the 3ʹ-UTR of its mRNA (Targetscan). LncRNAs have been well known to exert roles by acting as a competitive endogenous RNA (ceRNA) to segregate microRNAs (miRNAs) away from target mRNAs [15][16][17]. Therefore, we speculated that, exosomal KLF3-AS1 derived from MSCs might act as a ceRNA by sponging miR-206 to facilitate GIT1 expression, and thereby promote chondrocyte proliferation and inhibit chondrocyte apoptosis.…”

Glucose-6-phosphate dehydrogenase blockade potentiates tyrosine kinase inhibitor effect on breast cancer cells through autophagy perturbation

“…In the study of autophagy flux, inhibition of lysosomal degradation by chloroquine or bafilomycin A causes accumulation of both LC3-II and p62, and this reflects the amount of LC3-II and p62 that would have been degraded by autophagy over the treatment period [50][51][52]. In Fig.…”

SATB1 3′‐UTR and lncRNA‐UCA1 competitively bind to miR‐495‐3p and together regulate the proliferation and invasion of gastric cancer

“…18,19 However, little study has investigated the regulatory effect of mRNA on lncRNA through sponging miRNA. 18,19 However, little study has investigated the regulatory effect of mRNA on lncRNA through sponging miRNA.…”

“…However, growing evidence suggests that lncRNAs and miRNAs play crucial roles in various biological processes but their expression dysregulation is also implicated in regulating or coordinating diverse pathologies (eg, cancer). 18,19 However, the ceRNA hypothesis also provide a possibility that other RNA transcripts may conversely influence the expression or function of lncRNAs through competitively combining with miRNA. [7][8][9][10][11][12] As increased lncRNA-UCA1 is associated with poor overall survival and disease-free survival of GC patients, lncRNA-UCA1 has been suggested as a promising biomarker for the early detection and prognosis prediction.…”