Long non‐coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR‐345‐5p/RACGAP1‐mediated mitochondrial fission

Abstract

Long non-coding RNAs (lncRNAs) are emerging as key molecules in various cancers, yet their potential roles in the pathogenesis of breast cancer are not fully understood. Herein, using microarray analysis, we revealed that the lncRNA RACGAP1P, corresponding to the pseudogene of Rac GTPase Activating Protein 1 (RACGAP1), is up-regulated in breast cancer tissues. Its high expression was confirmed in 25 pairs of breast cancer tissues and 8 breast cell lines by qRT-PCR. Subsequently, we found that RACGAP1P expression was positively correlated with lymph node metastasis, distant metastasis, TNM stage, and shorter survival time in 102 breast cancer patients. Then, in vitro and in vivo experiments were designed to investigate the biological function and regulatory mechanism of RACGAP1P in breast cancer cell lines. Overexpression of RACGAP1P in MDA-MB-231 and MCF7 breast cell lines increased their invasive ability and enhanced their mitochondrial fission. Conversely, inhibition of mitochondrial fission by Mdivi-1 could reduce the invasive ability of RACGAP1P-overexpressing cell lines. Furthermore, the promotion of mitochondrial fission by RACGAP1P depended on its

Mitochondrial Fission and Fusion in Tumor Progression to Metastasis

“…Two recent studies look at how RAC GTPase activation protein 1 (RACGAP1) influences metastasis through ERK dependent mitochondrial fission and quality control ( Ren et al, 2021 ; Zhou et al, 2021 ). RACGAP1 contains a conserved Rho GAP domain which facilitates the inactivation of small GTPases of the Rho family including RAC1, CDC42, and RHOA ( Touré et al, 1998 ).…”

“…This suggests the importance of ERK1/2 in mediating mitochondrial fission to promote tumor cell invasion. In a follow up study, authors used breast cancer models to investigate the role of lncRNA, RACGAP1P, which acts as an endogenous competitor for a microRNA that degrades RACGAP1 ( Wang et al, 2019b ; Zhou et al, 2021 ). RACGAP1P was expressed higher in tumorigenic tissues in comparison to matched normal tissues.…”

Overexpression of lncRNA SLC16A1-AS1 Suppresses the Growth and Metastasis of Breast Cancer via the miR-552-5p/WIF1 Signaling Pathway

“…With the development of high-throughput sequencing technologies, over 80% of genes are identified to be non-coding RNAs in the human genome, such as lncRNAs and miRNAs, which were initially thought to be transcriptional "noise" (24,25). Accumulated studies have reported that lncRNAs are critical in BC progression, and have focused on discovering novel diagnostic, therapeutic, and prognostic targets for BC from lncRNAs (26)(27)(28).…”

circRPS28 (hsa_circ_0049055) is a novel contributor for papillary thyroid carcinoma by regulating cell growth and motility <i>via</i> functioning as ceRNA for miR-345-5p to regulate frizzled family receptor 8 (FZD8)

“…FZD8 was here identified as a new target functional gene in PTC. Besides, miR-345-5p could exert antiproliferation and anti-metastasis role in other human cancers, such as breast cancer [26], gastric cancer [27], and pancreatic cancer [17]. MiR-345-5p, sponged by circPRS28, was a direct regulator of functional gene FZD8 in development of PTC cells.…”