TY - JOUR
T1 - Hypoxia stimulates the cytoplasmic localization of oncogenic long noncoding RNA LINC00152 in colorectal cancer
AU - Nishizawa, Yujiro
AU - Konno, Masamitsu
AU - Asai, Ayumu
AU - Koseki, Jun
AU - Kawamoto, Koichi
AU - Miyoshi, Norikatsu
AU - Takahashi, Hidekazu
AU - Nishida, Naohiro
AU - Haraguchi, Naotsugu
AU - Sakai, Daisuke
AU - Kudo, Toshihiro
AU - Hata, Taishi
AU - Matsuda, Chu
AU - Mizushima, Tsunekazu
AU - Satoh, Taroh
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Funding Information:
We thank the members of our laboratories for their helpful discussions. We thank Drs Tamura and Ikenaga for the careful arrangement of clinical samples; Dr Yamamoto, Division of Health Sciences, Osaka University, and Dr Takemasa, Department of Surgery, Sapporo Medical University, for fruitful discussions. This study was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and Ministry of Health, Labor and Welfare; and by a grant from the National Institute of Biomedical Innovation and Osaka University Drug Discovery Funds. Institutional endowments were received partially from Taiho Pharmaceutical Co., Ltd., Evidence-Based Medical (EBM) Research Center, Idea Consultants, Inc. (Tokyo, Japan), and Kinshu-kai Medical Corporation (Osaka, Japan) [to Y.D., M.M. and H.I.]; Chugai Co., Ltd., Yakult Honsha Co., Ltd., and Merck Co., Ltd. [to Y.D., M.M. and T.S.]. These funders had no role in the main experimental equipment, supply expenses, study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study received financial support from grants-in-aid for Scientific Research and P-DIRECT and P-CREATE grants from the Ministry of Education, Culture, Sports, Science and Technology, MEXT (to M.K., N.N., Y.D., M.M. and H.I.); Kobayashi Foundation for Cancer Research (to H.I.); Kobayashi International Scholarship Foundation (to M.K. and H.I.); a Grant-in-Aid from the Ministry of Health, Labor, and Welfare (to M.K., Y.D., M.M. and H.I.); and a Grant-in-Aid for Young Scientists (B) (Japan Society for the Promotion Science KAKENHI grant no. 17K16549) (to Y.N.).
PY - 2018/2
Y1 - 2018/2
N2 - Recent studies have indicated that long noncoding RNAs (lncRNAs) play a pivotal role in almost all physiological cellular processes, including every stage of cancer development. Given that hypoxia in the tumor microenvironment is involved in the malignant behavior of tumors, such as invasion and metastasis, we investigated the cytoplasmic and nuclear localization of lncRNAs in colorectal cancer cells. A cell culture under hypoxic conditions revealed several lncRNAs, such as LINC00152, whose levels were increased in the cytoplasm of colorectal cancer cells. A database study indicated that LINC00152 shares microRNA-binding sites, such as miR-138 and miR-193, with the hypoxia-inducible factor 1 (HIF1), thus suggesting that LINC00152 could possibly function as a competing endogenous RNA that can augment Hif1 translation in the cytoplasm of hypoxic colorectal cancer cells. Moreover, the data presented in the studies of surgically resected samples showed that patients with colorectal cancer exhibiting high LINC00152 expression were associated with a worsened survival rate; this supports the suggested oncogenic function of LINC00152 in the cytoplasm under hypoxic conditions. The present study demonstrated that lncRNA networks could provide diagnostic tools and novel therapeutic targets against colorectal cancer cells.
AB - Recent studies have indicated that long noncoding RNAs (lncRNAs) play a pivotal role in almost all physiological cellular processes, including every stage of cancer development. Given that hypoxia in the tumor microenvironment is involved in the malignant behavior of tumors, such as invasion and metastasis, we investigated the cytoplasmic and nuclear localization of lncRNAs in colorectal cancer cells. A cell culture under hypoxic conditions revealed several lncRNAs, such as LINC00152, whose levels were increased in the cytoplasm of colorectal cancer cells. A database study indicated that LINC00152 shares microRNA-binding sites, such as miR-138 and miR-193, with the hypoxia-inducible factor 1 (HIF1), thus suggesting that LINC00152 could possibly function as a competing endogenous RNA that can augment Hif1 translation in the cytoplasm of hypoxic colorectal cancer cells. Moreover, the data presented in the studies of surgically resected samples showed that patients with colorectal cancer exhibiting high LINC00152 expression were associated with a worsened survival rate; this supports the suggested oncogenic function of LINC00152 in the cytoplasm under hypoxic conditions. The present study demonstrated that lncRNA networks could provide diagnostic tools and novel therapeutic targets against colorectal cancer cells.
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U2 - 10.3892/ijo.2017.4218
DO - 10.3892/ijo.2017.4218
M3 - Article
C2 - 29345294
AN - SCOPUS:85040320457
SN - 1019-6439
VL - 52
SP - 453
EP - 460
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 2
ER -
