MicroRNA-224 aggrevates tumor growth and progression by targeting mTOR in gastric cancer

Abstract

Abstract. Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumors, including gastric cancer. Aberrant miR-224 expression has been indicated in tumor growth, the mechanism of miR-224 promoting the proliferation and metastatic ability for gastric cancer remains unclear. Accumulating evidence reports that mTOR signal pathway plays an important role in the cellular process, such as apoptosis, cell growth and proliferation. The goal of the present study was to identify whether miR-224 could inhibit the growth, migration, invasion, proliferation and metastasis of gastric cancer through targeting mTOR expression. Real-time PCR (RT-PCR) was used to quantify miR-224 expression in vitro and in vivo experiments. Luciferase reporter assays were performed to confirm the activity of mTOR pathway, and immunofluorescence staining assay was conducted to observe apoptosis and cell proliferation ability. Bioinformatics as well as cell luciferase function studies distinguished the direct modulation of miR-224 on the 3'-UTR of the mTOR, which leads to the inactivation of apoptosis signaling and the activation of cell proliferation. In addition, inhibition of miR-224 significantly reduced the expression of mTOR and improved caspase-9/3 expression while decreased cyclin D1/2 levels, attenuating gastric cancer cell proliferation. Therefore, the present study revealed the mechanistic links between miR-224 and mTOR in the pathogenesis of gastric cancer through modulation of caspase-9/3 and cyclin D1/2. In addition, targeting miR-224 could serve as a novel strategy for future gastric cancer therapy.

Protective effect of microRNA‐224 on acute lower extremity ischemia through activation of the mTOR signaling pathway via CHOP in mice

“…Besides, miR-224 activates the mTOR signaling pathway in gastric cancer cell lines inhibiting apoptosis in vitro (Y. Zhang et al, 2016).…”

Tanshinone IIA suppresses gastric cancer cell proliferation and migration by downregulation of FOXM1

“…Abnormal proliferation and migration of tumor cells are crucial pathological processes involved in malignant tumors (13–16). Tumor metastasis is a complex process which includes migratory tumor cells leaving the primary tumor by invasion, disseminating throughout the body via the circulatory system, and colonizing eventually at distant organs (17).…”

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

“…It has been established that an miRNA can have a predominantly oncogenic role in one type of cancer and a tumor suppressive role in another; for instance, miR-224 was identified to be a tumor suppressor in prostate cancer (30), whereas in other types of malignancy, including gastric (11,31) and colorectal cancer (32), an oncogenic role for miR-224 was described. The ambiguous role of miR-224 was also observed within the SCC histological subtype of NSCLC in the present study.…”