Psoralen Suppresses Cisplatin-Mediated Resistance and Induces Apoptosis of Gastric Adenocarcinoma by Disruption of the miR196a-HOXB7-HER2 Axis.
Purpose
The present study aimed to investigate the impact of psoralen on miR-196a-5p expression and function, and to reveal the mechanism underlying miR-196a-5p-mediated inhibition and the reversal of cisplatin (DDP) resistance.


Methods
Serum samples were collected from 50 patients with gastric cancer (GC), and the association between miR-196a-5p expression and the response to chemotherapy was assessed. A DDP-resistant GC cell line was also established to determine the effects of miR-196a-5p and psoralen on DDP resistance. MGC803 cells were transfected with miR-196a-5p mimic and inhibitor vectors for the overexpression and downregulation of miR-196a-5p, respectively.


Results
Clinical data analysis showed that the lower expression levels of miR-196a-5p were significantly associated with chemoresistance in patients with GC. Upregulation of miR-196a-5p significantly enhanced the anti-proliferative effect, apoptosis and sensitivity to DDP by regulating the protein expression levels of HOXB7, HER2, Bcl-2 and G1/S-specific cyclin-D1 (CCND1). Furthermore, psoralen reversed miR-196a-5p-induced DDP resistance and reduced the expression levels of HOXB7, HER2, Bcl-2 and CCND1.


Conclusion
miR-196a-5p may be a novel biomarker of chemotherapeutic success in patients with GC and may also influence the sensitivity of GC cells to DDP. Moreover, psoralen can increase chemotherapeutic sensitivity by upregulating miR-196a-5p and then downregulating HOXB7-HER2 signaling axis.
['Jin|Lei|L|0000-0002-0752-7628', 'Ma|Xue-Mei|XM|', 'Wang|Ting-Ting|TT|', 'Yang|Yao|Y|', 'Zhang|Nan|N|', 'Zeng|Na|N|', 'Bai|Zhi-Gang|ZG|', 'Yin|Jie|J|', 'Zhang|Jun|J|', 'Ding|Guo-Qian|GQ|', 'Zhang|Zhong-Tao|ZT|']
psoralen miR-196a-5p cisplatin gastric cancer chemoresistance HOXB7