Cell type-specific reciprocal regulation of HIF1A gene expression is dependent on 5'- and 3'-UTRs.
In the present study, we demonstrated the reciprocal regulation of hypoxia-inducible factor 1 alpha (HIF1A) gene expression via untranslated region-(UTR) dependent mechanisms. A 151 nucleotide sequence found in the HIF1A 5'-UTR is sufficient for significant translational up-regulation. On the other hand, the 3'-UTR of HIF1A has been implicated in mRNA degradation. In the non-metastatic breast cancer cell line MCF7, the 3'-UTR-dependent down-regulatory machinery predominates over the 5'-UTR-dependent up-regulation of HIF1A. However, 5'-UTR-dependent up-regulation is dominant among metastatic cell lines (MDA-MB453, U87MG). It is therefore likely that the predominance of 5'-UTR-dependent translational enhancement of HIF1A is critical for the malignant phenotype of cancer cells. PTBP-1, but not HuR, is a candidate RNA binding protein for the translational control of HIF1A.
Department of Oral Pathobiology, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-ku, Sapporo 060-8586, Japan.
Motoaki
M
Yasuda
Department of Oral Pathobiology, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-ku, Sapporo 060-8586, Japan.
Tomoyuki
T
Hatanaka
Department of Radiation Medicine, Hokkaido University School of Medicine, K15 W7, Kita-ku, Sapporo 060-8638, Japan.
Hiroki
H
Shirato
Department of Biomedical Sciences and Engineering, Graduate School of Health Sciences, Hokkaido University, N12 W5, Kita-ku, Sapporo 060-0812, Japan. Electronic address: trout@hs.hokudai.ac.jp.
Takeshi
T
Nishioka
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D015854:Up-Regulation
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D008156:Luciferases
HIF-1α; Hypoxia; Transcription; Translation; UTR