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

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: LAMB3; PI3K/AKT signaling pathway; cell proliferation; cervical cancer; hsa-mir-133a-2.