MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2

Abstract

Background/Aims: Lung cancer is one of the most common causes of cancer related deaths worldwide. The role of several microRNAs (miRNAs) including miR-196b in different cancers has already been established. The study was aimed to explore the role of miR-196b in lung cancer and its possible underlying mechanism. Methods: Human lung cancer cell line A549 was transfected with miR-196b mimic, miR-196b inhibitor and corresponding controls. Then cell viability, migration, invasion, and apoptosis of A549 lung cancer cells either with overexpression or with suppression of miR-196b were estimated sequentially. Next, dual luciferase activity assay was performed to clarify whether Runx2 was a direct target of miR-196b. Finally, the expressions of main factors associated with epithelial mesenchymal transition (EMT), PI3K/AKT/GSK3β, Smad, and JNK pathways were detected by western blot. Results: MiR-196b expression was significantly decreased in A549, H1650 and H1299 cell lines compared with in WI-38 and HEL-1 cell lines. Overexpression of miR-196b suppressed cell viability, migration, invasion, and induced apoptosis as well as inhibited TGF-β induced EMT process in A549 cells. In addition, Runx2 was a putative target of miR-196b, and Runx2 silence remarkably increased cell apoptosis and abolished the promotive effects of miR-196b suppression on cell viability, migration and invasion. Finally, miR-196b also mediated its action by inactivation of PI3K/AKT/GSK3β, Smad, and JNK pathways by down-regulation of Runx2. Conclusion: MiR-196b functions as a tumor suppressor that inhibited cell growth and metastasis of lung cancer cells by targeting Runx2. These findings provided further evidences for treatment of lung cancer.

MicroRNA‑18b acts as an oncogene in gastric cancer by directly targeting Kruppel‑like factor 6

“…Previous studies have reported that miRNAs modulate the expression of >50% of human protein-coding genes involved in the regulation of a wide range of physiological and pathological processes, including cell proliferation, cycle, apoptosis, differentiation, metabolism and tumorigenesis (8). Several miRNAs have been demonstrated to be aberrantly expressed in the majority of human malignancies (9)(10)(11). Abnormally expressed miRNAs may result in the progression or inhibition of normal cell growth patterns, thus leading to cancer initiation and progression (12).…”

miR‑552‑5p facilitates osteosarcoma cell proliferation and metastasis by targeting WIF1

“…Scholars reported that miRNAs function in different types of human cancer. For example, Bai et al (11) revealed that miRNA-196b suppressed cell metastasis and proliferation by inhibiting Runx2 in lung cancer. Wang et al (12) reported that miR-101 suppressed proliferation and migration of breast cancer cells by targeting SOX2.…”

RUNX2 Plays An Oncogenic Role in Esophageal Carcinoma by Activating the PI3K/AKT and ERK Signaling Pathways

“…For instance, RUNX2 is abnormally expressed in highly metastatic prostate cancer cells and may function as a key regulator in prostate cancer metastatic bone disease [12,13]. Targeting of RUNX2 is found to impair the progression of breast cancer to metastatic bone disease [14] and repress cell growth and metastasis of lung cancer cells [15]. In addition, RUNX2 can promote the metastasis of human gastric cancer through up-regulation of the chemokine receptor CXCR4 [16].…”