Abstract

 
 
 
 Purpose: To investigate the role of miR-449b-5p in gastric cancer (GC) metabolism.
 Methods: Human GC samples and their corresponding normal tissues were used in this study. Cell survival ability was evaluated using a commercial MTT kit. Glucose uptake, lactate production and ATP content were assessed using commercial kits. The expression levels of miRNAs were assessed by stem-loop reverse transcription-polymerase chain reaction (RT-PCR).
 Results: MiR-449b-5p expression decreased in both GC tissues and cells. When the cells with low level of miR-449b-5p were transfected with miR-449b-5p mimics, glycolysis was inhibited (p < 0.05). Lactate dehydrogenase A (LDHA) was predicted as a target gene of miR-449b-5p and verified using luciferase reporter assay. MiR-449b-5p expression was up-regulated in GC cells (p < 0.05). Furthermore, miR- 449b-5p expression was related to long overall survival time in patients with GC.
 Conclusion: The findings demonstrate that miR-449b-5p reverses the glycolytic state of GC cells by targeting LDHA expression, and thus, it can potentially be developed for the treatment of gastric cancer.
 
 
 
Highlights
Gastric cancer (GC) is a type of cancer of the digestion system
To identify the miRNAs that negatively regulate human Lactate dehydrogenase A (LDHA) in GC, individual miRNAs were transfected into MGC-803 cells and LDHA mRNA expression was tested by real time RTPCR
The results showed that the levels of miR-449b-5p were significantly lower in GC samples than the adjacent normal samples (Figure 1 B and C)
Summary
The major reasons for therapy failure in patients with GC include metastasis, chemotherapy drug resistance, tumor microenvironment and the glycolytic state [1]. There is a high glycolytic state in GC tissues and many studies focus on cancer cell metabolism in order to find a new therapeutic method. There are still unknown pathological mechanism of GC for further investigation including, cancer cell glycolysis. Some molecules involved in glycolysis such as LDHA is an important transcription factor related to tumor growth, resistance, metastasis and glycolysis [9], epigenetic therapy such as miRNAs for LDHA in GC is still unclear. To assess the underlying mechanism of LDHA involved in GC glycolysis, biological informatics was used to predict miRNAs that might regulate LDHA expression. The new selected miR-449b-5p regulating LDHA will be further investigated to determine the molecular of action mechanism in GC
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