Human chorionic gonadotropin (hCG) a sialoglycoprotein hormone composed of two noncovalently linked subunits - a (hCGa) and ß (hCGß) is physiologically produced by trophoblastic cells of the placenta. Recent studies demonstrated that besides of placenta the hCG and especially its ß-subunit is secreted by malignant trophoblastic tumors, as well as by a varieties of tumors of different origin. The role of hCG in tumorogenesis is unknown but it is suggested that hCGß can stimulate growth of cancer cells or inhibit the apoptosis.

Selective downregulation the expression of particular gene allows researchers to determinate its function in many cellular processes. Targeting the mRNA transcripts of a specific gene with antisense RNA, ribozyme or siRNA has shown variable success.

In our recent study we applied an alternative approach for reducing the mRNA output of target gene based on a modified U1 snRNA. Previously we showed that the active hCGß gene is present in nontrophoblastic gynecological cancers tissue. Here we used the property of U1 snRNA to block the accumulation of specific RNA transcript when it binds to its donor sequence within the terminal exon as an effective method for inactivating beta subunit of human chorionic gonaotropin gene in HeLa cell line. The first 10 nucleotides of the human U1 snRNA gene, which normally binds to 5’ss in pre-mRNA were replaced by a sequence complementary to a 10-nt segment in the terminal exon of the hCGß mRNA.

The 5’ end-muted U1 snRNAs block the expression of hCGß in cervix carcinoma cell line what was showed by immunohistochemistry. hCG was undetectable in cancer cells expressing U1 constructs. Further analysis showed that knocking down the gonadotropin expression significantly increases the apoptosis rate. Almost 95% all cells expressing a modified U1 sn RNAs showed morphological changes characteristic for apoptotic process.

The result of the study showed that the possibility to effectively block the hCGß expression, could lead to a new way to treat patients with gynecological cancers.

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