Abstract
Cisplatin-based chemotherapy is the most commonly used treatment regimen for gastric cancer (GC), however, the resistance to cisplatin represents the key limitation for the therapeutic efficacy. Aberrant expression of MiR-524-5p appears to be involves in tumorigenesis and chemoresistance. However, the mechanism by which miR-524-5p mediates effects of cisplatin treatment in GC remains poorly understood. Expressions of MiR-524-5p was detected in GC tissues and cell lines by qRT-PCR. Cell proliferation was observed by MTT assay; Cell migration was detected by transwell migration and invasion assay. The targeting protein of miR-524-5p was identified by luciferase reporter assay and western blot. We found that downregulation of miR-524-5p in GC tissues and cell lines. SC-M1 and AZ521 cells resistant to cisplatin expressed low levels of miR-524-5p in comparison to the sensitive parental cells. Overexpression of miR-524-5p expression in SC-M1 and AZ521 cells inhibited cell proliferation, migration, and invasion, and conferred sensitivity to cisplatin-resistant GC cells. Subsequently, we identified SOX9 as a functional target protein of miR-524-5p and found that SOX9 overexpression could counteracts the chemosensitizing effects of miR-524-5p. These results provide novel insight into the regulation of GC tumorigenesis and progression by miRNAs. Restoration of miR-524-5p may have therapeutic potential against GC.
Highlights
Gastric cancer (GC) is one of the most frequent tumors and the second leading cause of cancer-related death worldwide, with East Asia accounting for more than half of the annual cases [1]
The results revealed that miR524-5p expression levels in gastric cancer (GC) tissues were significantly lower compared with those in healthy tissues, and 31/50 samples displayed a reduction of ≤ 50% (Figure 1A)
We found that low miR-524-5p expression was more frequently detected in GC patients with larger tumor size, positive lymph node metastasis, and advanced TNM stage
Summary
Gastric cancer (GC) is one of the most frequent tumors and the second leading cause of cancer-related death worldwide, with East Asia accounting for more than half of the annual cases [1]. It is estimated that the overall 5 years survival for GC patients is only 20% [2]. Metastasis is found in more than half of advanced GC patients and causes the majority of cancer-related mortalities [4,5]. Cisplatin is the most widely used first-line chemotherapeutic agent for GC. A large number of patients will develop cisplatin resistance which is associated with recurrence and metastasis [6]. Little improvement in longterm survival has been made in recent years, partly because of the chemotherapeutic drug resistance. It is of great importance to find new molecular markers that will help improve the sensitivity of GC cells to cisplatin
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