MiR-145-5p suppresses the proliferation, migration and invasion of gastric cancer epithelial cells via the ANGPT2/NOD_LIKE_RECEPTOR axis

Abstract

Objective: This study aimed to investigate the relationship among miR-145-5p, ANGPT2 and the NOD_LIKE_RECEP-TOR pathway, thereby revealing the molecular mechanism of these three factors underlying the proliferation, migration and invasion of gastric cancer (GC) epithelial cells. Methods: qRT-PCR was carried out to detect the expression of miR-145-5p and ANGPT2 mRNA. Western blot was performed to test the protein levels of ANGPT2 as well as NOD1, NOD2 and NF-κB in the NOD_LIKE_RECEPTOR pathway. The targeting relationship between miR-145-5p and ANGPT2 was verified via a dual-luciferase reporter gene assay. The proliferation, migration and invasion of GC cells were detected through MTT and Transwell assays, respectively. Results: The expression of miR-145-5p was significantly down-regulated in GC cells, while that of ANGPT2 was notably up-regulated. MiR-145-5p directly bound with the 3′-UTR of ANGPT2 mRNA, thereby targeting ANGPT2 after transcription. Overexpression of miR-145-5p inhibited the proliferation, migration and invasion of GC cells by suppressing ANGPT2. Moreover, low expression of ANGPT2 affected the protein levels of NOD1, NOD2 and NF-κB in the NOD_LIKE_RECEPTOR pathway, thus weakening the abilities of cell proliferation, migration and invasion. Conclusions: MiR-145-5p plays an important role in GC epithelial cells, and it can affect cell proliferation, migration and invasion of GC cells by targeting ANGPT2 and regulating the NOD_LIKE_RECEPTOR pathway. Overall, our study further elucidates the molecular mechanism underlying the malignant progression of GC.

MicroRNA miR-145-5p inhibits Phospholipase D 5 (PLD5) to downregulate cell proliferation and metastasis to mitigate prostate cancer

“…In assessing tumor repression mechanism, the present study hypothesized a regulation of PCa biological activities via corresponding genes’ modulation. Previous investigations have outlined genes such as MYO6 [ 31 ], ANGPT2 [K. 32 ], and TGF-β1 [Y. 33 ] as the ultimate target of miR-145.…”

Comprehensive Genomic Characterization Analysis Identifies an Oncogenic Pseudogene RP11-3543B.1 in Human Gastric Cancer

“…Interestingly, in addition to RP11-354B3.1, we found that miR-145-5p and one of its’ target genes MAPK4 were listed in the top candidates ( Figure 5A ). Combined with the above GSEA analysis results, we chose miR-145-5p and MAPK4 for further validation because several studies had revealed the tumor suppressive function of miR-145-5p in GC cells ( Li et al, 2020 ; Zhou et al, 2020 ). More importantly, MAPK4 is key regulator in the JNK and ERK signaling pathway.…”

Circular RNA circDNM3OS Functions as a miR-145-5p Sponge to Accelerate Cholangiocarcinoma Growth and Glutamine Metabolism by Upregulating MORC2

“…Many researches had revealed that miR-145-5p exerted an inhibitory impact on a series of tumor growth. 26–28 Zhou et al marked that miR-145-5p repressed cell invasion, migration, and proliferation of gastric cancer cells through targeting ANGPT2 and modulating the NOD_LIKE_RECEPTOR pathway. 26 Moreover, circRNA circ_0058063 sponged miR-145-5p to elevate CDK6 expression, thereby accelerating cell migration and growth in bladder cancer.…”

“… 26–28 Zhou et al marked that miR-145-5p repressed cell invasion, migration, and proliferation of gastric cancer cells through targeting ANGPT2 and modulating the NOD_LIKE_RECEPTOR pathway. 26 Moreover, circRNA circ_0058063 sponged miR-145-5p to elevate CDK6 expression, thereby accelerating cell migration and growth in bladder cancer. 27 Furthermore, miR-145-5p played a suppressive effect on hepatocellular cancer growth.…”