Abstract
Higher Lin28 expression is associated with worse pathologic tumor responses in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. However, the characteristics of Lin28 and its mechanism of action in chemotherapy resistance is still unclear. In this study, we found that transfection of Lin28 into gastric cancer cells (MKN45 and MKN28) increased their resistance to the chemo-drugs oxaliplatin (OXA), paclitaxel (PTX), doxorubicin (ADM), and fluorouracil (5-Fu) compared with gastric cancer cells transfected with a control vector. When knockdown Lin28 expression by Lin28 small interfering RNA (siRNA) was evaluated in vitro, we found that the resistance to chemo-drugs was reduced. Furthermore, we found that Lin28 up-regulates C-myc and P-gp and down-regulates Cylin D1. Finally, we found that miR-107 is a target microRNA of Lin28 and that it participates in the mechanism of chemotherapy resistance. Our results suggest that the Lin28/miR-107 pathway could be one of many signaling pathways regulated by Lin28 and associated with gastric cancer chemo-resistance.
Highlights
Gastric cancer is a common clinical digestive system malignant tumor with a mortality rate that ranks third in the world [1]
We identified gastric cancer cells with stable Lin28 expression from resistant transfected clones (MKN45/Lin28/C2 and MKN28/Lin28/C3) using western blotting and q-Polymerase Chain Reaction (PCR) (Fig 1)
We investigated the association of Lin28 expression with chemo-sensitivity in gastric cancer cells
Summary
Gastric cancer is a common clinical digestive system malignant tumor with a mortality rate that ranks third in the world [1]. Our country is an area that is prone to gastric cancer. Neo-adjuvant chemotherapy has been administered to gastric cancer patients to prolong survival. The 5-year survival rate of those with advanced gastric cancer is still lower than 30% [2]. Chemotherapy resistance is the leading cause of the failure of gastric cancer and other tumor treatments. The mechanism of chemotherapy resistance of gastric cancer is currently a major concern in gastric cancer studies
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