Hammerhead ribozyme targeting human hypoxia inducible factor-1alpha gene effectively attenuates HeLa xenograft tumors.
BACKGROUND
Hypoxia inducible factor l is a heterodimeric transcription factor that plays an important role in oxygen homeostasis. A good body of evidence indicates that overexpression of HIF-1alpha driven by intratumoral hypoxia can transactivate genes essential for energy metabolism, erythropoiesis, and vascular development, which is directly involved in cancer progression. Overexpressed HIF-1alpha also has a considerably reversed clinical correlation with treatment efficacy as well as mortality of cancers.


METHODS
We took the advantage of the hammerhead ribozyme that specifically targeted 1762-1778 nt of HIF-1alpha messenger RNA.


RESULTS
The designed ribozyme could cleave its substrate HIF-1alpha messenger RNA in both in vitro and in intracellular cleavage assays. More interesting, the synthetic ribozyme RNA administered to HeLa xenograft large tumor could effectively inhibit its angiogenesis and tumor growth.


CONCLUSIONS
It is reasonable to speculate that down-regulation of HIF-1alpha activity could be a potential mechanism useful to prevent survival or angiogenic activity of various solid tumors.
Department of Neuronal Surgery, The Affiliated Hospital of Xuzhou Medical College, China. sq56_2008@126.com
Rutong
R
Yu
Rui
R
Chen
Qiong
Q
Shi
Ting
T
Li
Hong
H
Tang
D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D016133:Polymerase Chain Reaction; D016337:RNA, Catalytic / Q000378:metabolism / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000628:therapy*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016337:RNA, Catalytic; C427204:hammerhead ribozyme