miR-145 suppresses the proliferation, invasion and migration of NSCLC cells by regulating the BAX/BCL-2 ratio and the caspase-3 cascade

Abstract

Although microRNA (miR)-145 has been identified to be a tumor suppressor in various types of tumor, it promotes the progression of non-small cell lung cancer (NSCLC). However, the precise underlying molecular mechanism of its action remains unclear. The present study investigated the effects of miR-145 on the proliferation, invasion, metastasis and apoptosis of the NSCLC A549 cell line and the underlying molecular mechanism of its action. In vitro cell proliferation, invasion, migration and apoptosis assays were employed, and the expression levels of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3and poly(ADP-ribose) polymerase (PARP) were evaluated by western blot analysis. The results demonstrated that ectopic expression of miR-145 inhibited the proliferation, invasion and migration of A549 cells, but promoted the apoptosis of A549 cells. Western blot analysis indicated that increased miR-145 levels led to a marked decrease in the expression of MMP-2, MMP-9 and Bcl-2. Upregulation of miR-145 expression increased the expression of Bax, thus increasing the Bax/Bcl-2 ratio. Additionally, the results indicated that miR-145 over expression promoted the cleavage of caspase-3 and PARP. Taken together, these results indicated that miR-145 suppresses the proliferative, invasive and migratory ability of A549 cells. Additionally, miR-145 upregulation induced apoptosis of A549 cells possibly by decreasing MMP-2 and MMP-9 expression, the Bax/Bcl-2 ratio and the activity of the caspase-3 cascade.

Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

“…Thus, the BAX/BCL‐2 ratio is a key regulator of apoptosis in lung cancer . Furthermore, caspase‐3, a member of the cysteine protease family, catalyzes crucial steps in apoptotic cell death . In this study, SCU increased the BAX/BCL‐2 ratio and the amount of cleaved caspase‐3 in A549 cells.…”

“…Flow cytometry was used to externalize phosphatidylserine (cell surface changes) in A549 cells and our results show that the percentage of apoptotic cells is markedly increased in a concentration‐dependent manner. Decreasing the level of the anti‐apoptotic BCL‐2 protein and/or increasing the level of the pro‐apoptotic BAX protein plays an important role in disrupting mitochondrial homeostasis, which can lead to apoptotic cell death . Thus, the BAX/BCL‐2 ratio is a key regulator of apoptosis in lung cancer .…”

Targeting dipeptidyl peptidase 8 genes inhibits proliferation, migration and invasion by inhibition of cyclin D1 and MMP2MMP9 signal pathway in cervical cancer

“…DPP8 upregulates the number of early apoptotic cells by interacting with Bcl‐2/Bax. As a key effector in cellular apoptosis, the B‐cell lymphoma 2 gene can block the apoptosis of some cells, such as lymphocytes, lung cancer cells and breast cancer cells . BCL‐2‐associated X protein can promote apoptosis and is a member of the Bcl‐2 gene family.…”

Identification of a mitochondrial‐targeting secretory protein from Nocardia seriolae which induces apoptosis in fathead minnow cells

“…(Figure f). And high Bax / Bcl ‐ 2 ratio is related to cell apoptosis (Pan et al, ). All these quantitative assays of ΔΨm value, caspase‐3 activity and mRNA expression of apoptosis‐related genes indicated that cell apoptosis could be induced by the overexpression of MTSP3141 or MTSP3141△TP in FHM cells.…”