Inhibition of lactate dehydrogenase A by microRNA‑34a resensitizes colon cancer cells to 5‑fluorouracil

Li,Xiangyong; Zhao,Haibin; Zhou,Xijian; Song,Lei

doi:10.3892/mmr.2014.2726

Inhibition of lactate dehydrogenase A by microRNA‑34a resensitizes colon cancer cells to 5‑fluorouracil

Authors:
- Xiangyong Li
- Haibin Zhao
- Xijian Zhou
- Lei Song
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Affiliations: Department of Hematology and Oncology, The 101st Hospital of the People's Liberation Army, Wuxi, Jiangsu 214044, P.R. China, Department of Pathology, The 101st Hospital of the People's Liberation Army, Wuxi, Jiangsu 214044, P.R. China
Published online on: October 21, 2014 https://doi.org/10.3892/mmr.2014.2726
Pages: 577-582

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Abstract

5‑Fluorouracil (5‑FU) chemotherapy is widely used in the treatment of advanced colon cancer. However, the development of resistance to 5‑FU is a significant obstacle to successful treatment. MicroRNA‑34a (miR‑34a) has been reported to be downregulated in a number of tumor types and has also been shown to act as a tumor suppressor. However, the mechanisms underlying the biological effects of miR‑34a in chemoresistance remain unclear. The present study showed that the expression of miR‑34a is downregulated in 5‑FU‑resistant colon cancer cells. In addition, 5‑FU‑resistant colon cancer cells exhibited upregulation of lactate dehydrogenase A (LDHA) expression and activity compared with parental cells. Furthermore, LDHA was shown to be a direct target of miR‑34a. Overexpression of miR‑34a reduced the expression of LDHA, probably through binding to the 3' untranslated region, leading to the re‑sensitization of 5‑FU‑resistant cancer cells to 5‑FU. Additionally, overexpression of LDHA rendered colon cancer cells resistant to 5‑FU, suggesting that the miR‑34a‑induced sensitization to 5‑FU is mediated through the inhibition of LDHA. In conclusion, the current study showed that miR‑34a is involved in sensitivity to 5‑FU in part through its effects on LDHA expression. This indicates that miR‑34a‑mediated inhibition of glucose metabolism may be a therapeutic target in patients with chemoresistant colon cancer.

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