In vitro and in vivo studies on the association of long non‑coding RNAs H19 and urothelial cancer associated 1 with the susceptibility to 5‑fluorouracil in rectal cancer

Yokoyama,Yasuyuki; Sakatani,Takashi; Wada,Ryuichi; Ishino,Kousuke; Kudo,Mitsuhiro; Koizumi,Michihiro; Yamada,Takeshi; Yoshida,Hiroshi; Naito,Zenya

doi:10.3892/ijo.2019.4895

In vitro and in vivo studies on the association of long non‑coding RNAs H19 and urothelial cancer associated 1 with the susceptibility to 5‑fluorouracil in rectal cancer

Authors:
- Yasuyuki Yokoyama
- Takashi Sakatani
- Ryuichi Wada
- Kousuke Ishino
- Mitsuhiro Kudo
- Michihiro Koizumi
- Takeshi Yamada
- Hiroshi Yoshida
- Zenya Naito
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Affiliations: Department of Integrated Diagnostic Pathology, Nippon Medical School Hospital, Tokyo 113‑8602, Japan, Department of Gastrointestinal and Hepato‑Biliary‑Pancreatic Surgery, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
Published online on: October 4, 2019 https://doi.org/10.3892/ijo.2019.4895
Pages: 1361-1371

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Abstract

There is no predictive biomarker for response to 5‑fluorouracil (5FU)‑based neoadjuvant chemotherapy (NAC) in rectal cancer. In the present study, we examined potential long non‑coding RNAs (lncRNAs) linked to the susceptibility to 5FU in cultured colorectal cancer cells, and in biopsy and resected tissues of 31 human rectal cancer cases treated with NAC. Candidate lncRNAs for the prediction of susceptibility to 5FU were investigated by comprehensive analysis of expression profiles of 84 lncRNAs in cultured cells using PCR array. Bioinformatic analysis identified H19 and urothelial cancer associated 1 (UCA1) as candidate biomarkers for 5FU susceptibility. Quantitative PCR of H19 and UCA1 in cultures of colorectal cancer cells demonstrated the notable variation in expression. The ratios of changes of H19 and UCA1 expression in response to 5FU were low in cells resistant to 5FU, whereas ratios were high in cells susceptible to 5FU. In 5FU‑susceptible cells, cell proliferation was inhibited by 5FU. Upregulation of H19 and UCA1 were associated with the reduction in target molecule expression, including retinoblastoma and p27kip1. In 31 cases of rectal cancer, H19 and UCA1 expression levels in biopsy and resected tissue were comparable. The ratios of H19 and UCA1 expression in resected tissue compared with biopsy samples were low in 17 cases, whereas the ratios were high in 14 cases; 11 of the 17 cases (65%) with low ratios exhibited poor response to NAC, whereas 4 of the 14 cases (29%) with high ratios showed poor response (P=0.045). The increase in H19 and UCA1 expression may represent the response to impaired cell cycle in cells susceptible to 5FU. Our results indicate that changes in H19 and UCA1 expression may be considered for predicting the susceptibility to 5FU‑based NAC in rectal cancer.

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