microRNA‑23a promotes cell growth and metastasis in gastric cancer via targeting SPRY2‑mediated ERK signaling

Abstract

microRNAs (miRs) serve important roles in various human cancer types. Recently, miR-23a has been indicated as an oncogene in gastric cancer, but the underlying mechanism remains unclear. In the present study, reverse transcription-quantitative polymerase chain reaction and western blot analysis was used to explore the effects of miR-23a in gastric cancer. Additionally, cell proliferation, migration and invasion were examined using an MTT assay, wound healing assay and Transwell assay, respectively. Furthermore, a luciferase reporter gene assay was used to confirm the target association. It was determined that miR-23a was significantly upregulated in gastric cancer tissues and cell lines compared with adjacent tissues, and a normal gastric epithelial cell line. Furthermore, its upregulation was significantly associated with cancer progression and poor prognosis of patients. Knockdown of miR-23a caused a notable reduction in the proliferation, migration and invasion of gastric cancer AGS cells. Sprouty homolog 2 (SPRY2) was then predicted to be target gene of miR-23a. A luciferase reporter gene assay data demonstrated that miR-23a has the ability to directly bind to the 3′-untranslational region of SPRY2 mRNA. Further investigation demonstrated that SPRY2 was significantly downregulated in gastric cancer tissues and cell lines, and the protein expression of SPRY2 was negatively regulated by miR-23a in AGS cells. Furthermore, knockdown of SPRY2 reduced the suppressive effects of miR-23a inhibition in AGS cell proliferation, migration and invasion. In addition, the activity of extracellular signal-regulated kinase (ERK) signaling was also inhibited by the miR-23a/SPRY2 knockdown in AGS cells. The present study indicated that miR-23a serves a promoting role in gastric cancer via targeting SPRY2 and downstream ERK signaling.

MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2

“…Similarly, a previous study has revealed that miR-23a was highly expressed in gastric cancer tissues and cell lines. 19 According to the examination, highly expressed miR-23a in cancers of the digestive system was associated with a poor prognosis. 20 Another study demonstrated that OC tissues had a high miR-23a expression, which was consistent with our findings.…”

The Sprouty/Spred family as tumor suppressors: Coming of age

“…In gastric cancer, low expression of Sprouty2 is associated with poor prognosis via the upregulation of FGFR2‐induced ERK activation, positive lymphatic invasion, and metastasis . MicroRNA‐23a, which is considered as an oncogene, is upregulated in gastric cancer samples and promotes cell proliferation and metastasis by targeting Sprouty2 . MicroRNA‐592 also enhances the proliferation and invasion of gastric cancer cells by targeting Sprouty2 .…”

“…40 MicroRNA-23a, which is considered as an oncogene, is upregulated in gastric cancer samples and promotes cell proliferation and metastasis by targeting Sprouty2. 67 MicroRNA-592 also enhances the proliferation and invasion of gastric cancer cells by targeting Sprouty2. 41 In esophageal squamous cell carcinoma, lncRNA CCAT1 is upregulated and induces the histone methylation of the promoter of Sprouty4, resulting in the suppression of Sprouty4 expression.…”

Overexpression of miR-331 Indicates Poor Prognosis and Promotes Progression of Breast Cancer

“…miR-23a was downregulated in endometrial cancer, which inhibited the development of endometrial cancer by targeting SIX1 [17]. In contrast, in gastric cancer, miR-23a was upregulated with the promoting role in gastric cancer through targeting SPRY2 [18]. For breast cancer, a variety of miRNAs have been reported to play roles in its development, which provide novel therapeutic targets for the treatment of breast cancer, such as miR-449b-5p, miR-141, miR-200c, which were overexpressed in breast cancer tissues and cell lines [19,20], and miR-216a, miR-223, miR-132-3p, which were downregulated [21][22][23].…”