<p>Promotion of miR-221-5p on the Sensitivity of Gastric Cancer Cells to Cisplatin and Its Effects on Cell Proliferation and Apoptosis by Regulating DDR1</p>

Abstract

Purpose: This research aimed to explore the role of miR-221-5p on the sensitivity of gastric cancer cells to cisplatin, and the proliferation and invasion of gastric cancer cells by regulating DDR1. Patients and Methods: Altogether 69 patients who treated with radical gastrectomy from January 2014 to January 2016 were collected. With the agree of the patients, 69 gastric carcinoma and 69 adjacent tissues were taken, respectively, during the operation, and gastric carcinoma and human gastric mucosa cells were purchased. RT-PCR was used for detection of the expression level of miR-221-5p and DDR1. Wound healing assay and CCK-8 assay were used for exploration of the cell migration and viability. Western blot and double luciferase reporter gene were performed to determine the target gene of miR-221-5p. Results: It was showed that miR-221-5p expression was decreased in GC tissues and cell lines. The high expression of miR-221-5p reduced the resistance of GC cells to cisplatin and inhibited the proliferation and migration of gastric cancer cells. The high expression of miR-221-5p promoted the proliferation, invasion and migration of GC cells. In addition, we found that DDR1 was a direct target gene of miR-221-5p in GC cells. We found that DDR1 expression increased in gastric carcinoma. Moreover, there was a negative correlation of DDR1 with the expression level of miR-221-5p. The increase of miR-221-5p increased the chemosensitivity of GC cells to cisplatin, and inhibited the proliferation, invasion, migration and EMT of GC cells by targeting DDR1. Conclusion: The above research indicated that miR-221-5p may be a target for enhancing cisplatin chemotherapy sensitivity in gastric cancer patients.

RNF185-AS1 promotes hepatocellular carcinoma progression through targeting miR-221-5p/integrin β5 axis

“…Luciferase reporter assay and RIP assay veri ed the prediction that RNF185-AS1 directly interacted with miR-221-5p. miR-221-5p has been reported to exerts tumor suppressive function in prostate cancer [17,18], gastric cancer [19] and colorectal cancer [20]. On the contrary, previous research have reported that miR-221-5p acted as an oncogene in several tumors, such as renal cell cancer [21], prostate cancer [22].…”

The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development

“…Moreover, a negative correlation between miR-221-5p and DDR1 has been demonstrated. Overexpression of miR-221-5p in gastric cancer cells inhibits not only EMT, but also proliferation and invasion through modulation of DDR1 expression [ 103 ]. DDR1 induces EMT in hepatocellular carcinoma by regulating STAT3 in vitro and in vivo [ 35 ].…”

“…In gastric cancer, miR-221-5p modulates DDR1 expression. When miR-221-5p is downregulated, DDR1 expression increases and promotes migration and invasion [ 103 ]. On the contrary, in pancreatic carcinoma, the interplay of DDR1 with E-cadherin and the Par3 signaling pathway was shown to prevent 3D invasion by enhancing cell–cell adhesion [ 114 ].…”

MicroRNAs as the critical regulators of cisplatin resistance in gastric tumor cells

“…It has been observed that there were significant miR-221-5p down regulations in GC tissues and cells. MiR-221-5p promoted apoptosis and cisplatin-sensitivity, while inhibited gastric tumor cell proliferation and migration through DDR1 targeting [ 50 ]. MET is also another RTK that is activated by hepatocyte growth factor (HGF) to regulate cell proliferation and survival.…”