hsa‐mir‐133a‐2 promotes the proliferation and invasion of cervical cancer cells by targeting the LAMB3‐mediated PI3K/ATK pathway

Abstract

Abstract Objective Cervical cancer, one of the common types of malignant tumors progressed in women, is on the rise in developing countries. Numerous previous studies have demonstrated that hsa‐mir‐133a‐2 miRNA is abnormally expressed in cervical cancer cells. However, its fundamental mechanism in cervical cancer needs to be further clarified. Our study set out to investigate the effect of hsa‐mir‐133a‐2 on the phenotypes of cervical cancer cells as well as any potential molecular processes involved in the proliferation and invasion of cervical cancer cells. Methods The Cancer Genome Atlas‐cervical squamous cell carcinoma and endocervical adenocarcinoma(TCGA‐CESC) was adopted in order to verify the expression of hsa‐mir‐133a‐2 in cervical cancer tissues and to identify its potential targets. The interaction between Laminin subunit beta‐3(LAMB3) and hsa‐mir‐133a‐2 was verified by TargetScan database as well as Luciferase reporter assay. The Cell Counting Kit‐8 (CCK8) and transwell methods were utilized to assess the influence of hsa‐mir‐133a‐2 on the proliferation and invasion characteristics of cervical cancer cells. We studied the role that hsa‐mir‐133a‐2 plays in cervical cancer progression through Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis as well as Western Blot (WB) experiment. Results Down‐regulation of hsa‐mir‐133a‐2 was detected in cervical cancer tissues. It directly targeted LAMB3 and negatively regulated LAMB3 expression. The overexpression of hsa‐mir‐133a‐2 has a significant inhibiting effect on cervical cancer cell proliferation and invasion. The overexpression of hsa‐mir‐133a‐2 significantly inhibits the proliferation and invasion of cervical cancer cells. Moreover, the LAMB3 was able to up‐regulate the phosphorylation levels of AKT and phosphatidylinositol 3‐kinase (PI3K) protein in cervical cancer cells. hsa‐mir‐133a‐2 could also modulate the PI3K/AKT signaling pathway by targeting LAMB3. Conclusion hsa‐mir‐133a‐2 inhibits cervical cancer cell proliferation and invasion by indirectly regulating the PI3K/AKT signaling pathway, providing us with a new clinical treatment strategy for cervical cancer.

Keywords

• cell proliferation
• cervical cancer
• hsa‐mir‐133a‐2
• LAMB3
• PI3K/AKT signaling pathway