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Mir-488 alleviates chemoresistance and glycolysis of colorectal cancer by targeting PFKFB3.


ABSTRACT:

Background

Considering the boosting effect of glycolysis on tumor chemoresistance, this investigation aimed at exploring whether miR-488/PFKFB3 axis might reduce drug resistance of colorectal cancer (CRC) by affecting glycolysis, proliferation, migration, and invasion of CRC cells.

Method

Totally, 288 CRC patients were divided into metastasis/recurrence group (n = 107) and non-metastasis/recurrence group (n = 181) according to their prognosis about 1 year after the chemotherapy, and their 3-year overall survival was also tracked. Besides, miR-488 expression was determined in peripheral blood of CRC patients and also in CRC cell lines (ie, W620, HT-29, Lovo, and HCT116). The targeted relationship between miR-488 and PFKFB3 was predicted by Targetscan software and confirmed by dual-luciferase reporter gene assay. Moreover, glycolysis and drug tolerance of CRC cells lines were assessed.

Results

MiR-488 expression was significantly decreased in metastatic/recurrent CRC patients than those without metastasis/recurrence (P < .05), and lowly expressed miR-488 was suggestive of unfavorable 3-year survival, large tumor size, poor differentiation, in-depth infiltration, and advanced Duke stage of CRC patients (P < .05). Besides, CRC cell lines transfected by miR-488 mimic demonstrated decreases in glucose uptake and lactate secretion, increases in oxaliplatin/5-Fu-sensistivity, as well as diminished capability of proliferating, invading, and migratory (P < .05), which were reversible by extra transfection of pcDNA3.1-PFKFB3 (ie, miR-488 mimic + pcDNA3.1-PFKFB3 group). Finally, the mRNA level of PFKFB3 was down-regulated by miR-488 mimic in CRC cell lines after being targeted by it (P < .05).

Conclusion

The miR-488/PFKFB3 axis might clinically refine chemotherapeutic efficacy of CRC, given its modifying glycolysis and metastasis of CRC cells.

SUBMITTER: Deng X 

PROVIDER: S-EPMC7843269 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Mir-488 alleviates chemoresistance and glycolysis of colorectal cancer by targeting PFKFB3.

Deng Xiaojing X   Li Dapeng D   Ke Xiquan X   Wang Qizhi Q   Yan Shanjun S   Xue Yongju Y   Wang Qiangwu Q   Zheng Hailun H  

Journal of clinical laboratory analysis 20200929 1


<h4>Background</h4>Considering the boosting effect of glycolysis on tumor chemoresistance, this investigation aimed at exploring whether miR-488/PFKFB3 axis might reduce drug resistance of colorectal cancer (CRC) by affecting glycolysis, proliferation, migration, and invasion of CRC cells.<h4>Method</h4>Totally, 288 CRC patients were divided into metastasis/recurrence group (n = 107) and non-metastasis/recurrence group (n = 181) according to their prognosis about 1 year after the chemotherapy, a  ...[more]

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