Knockdown of hTERT by siRNA inhibits cervical cancer cell growth in vitro and in vivo.
نویسندگان
چکیده
Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase that facilitates tumor cell invasion and proliferation. It has been reported that telomerase and hTERT are significantly upregulated in majority of cancers including cervical cancer, thus, downregulation of hTERT is a promising target in malignant tumor treatment. We established a short interfering RNA (siRNA) targeting hTERT, and transfected it into HeLa cells (a cervical cancer cell line) to investi-gate the effect of cell proliferation, apoptosis, migration and invasion in cervical cancer cells. The results showed that siRNA targeting hTERT could effectively knock down hTERT expression, remarkably suppress telomerase activity, cell proliferation, migration and invasion, and induced cell apoptosis of cervical cancers cells in vitro. In addition, we evaluated whether siRNA targeting hTERT affects tumor growth in nude mice, and found that it dramatically inhibited tumorigenesis and growth of mice injected with siRNA targeting hTERT. Furthermore, we also found that knockdown of hTERT was able to significantly suppress constitutive phosphorylation of Akt, PI3K, which might imply that reduction of hTERT inhibited tumor growth via the PI3K/Akt signaling pathway to some extent. These results suggest that the suppression of hTERT expression by siRNA inhibits cervical cancer cell growth in vitro and in vivo, and may provide a novel target for anticancer gene therapy.
منابع مشابه
Long non-coding RNA FOXO1 inhibits lung cancer cell growth through down-regulating PI3K/AKT signaling pathway
Objective(s): Lung cancer is one of the most common malignant tumors, which seriously threatens the health and life of the people. Recently, a novel long non-coding RNA (lncRNA) termed lncFOXO1 was found and investigated in breast cancer. However, the effect of lncFOXO1 on lung cancer is still ambiguous. The current study aimed to uncover the functions of lncFOXO1 in l...
متن کاملsiRNA-mediated inhibition of hTERC enhances radiosensitivity of cervical cancer.
BACKGROUND To investigate the influence of telomerase activity, apoptosis, radiosensitivity of cervical cancer after siRNA-mediated knockdown of telomerase RNA and evaluate in vivo growth with gene interference. METHODS We studied siRNA-targeting-telomerase RNA transfection into the Hela cell line. Expression of hTERC mRNA was detected by RT-PCR and telomerase activity was measured by the TRA...
متن کاملmiR-506 inhibits cell proliferation and invasion by targeting TET family in colorectal cancer
Objective(s): Ten-eleven translocation (TET) family members have been shown to be involved in the development of many tumors. However, the biological role of the TET family and its mechanism of action in colorectal carcinogenesis and progression remain poorly understood. Materials and Methods:We measured the expression levels of TET family members in colorectal cancer (CRC) specimens, in the c...
متن کاملDownregulation of Kinesin Spindle Protein Inhibits Proliferation, Induces Apoptosis and Increases Chemosensitivity in Hepatocellular Carcinoma Cells
Background: Kinesin spindle protein (KSP) plays a critical role in mitosis. Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately to cell death. The aim of this study was to suppress KSP expression by specific small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor activity. Methods: Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched-siRNA (...
متن کاملSilencing of the hTERT Gene by shRNA Inhibits Colon Cancer SW480 Cell Growth In Vitro and In Vivo
Human telomerase reverse transcriptase (hTERT) is the key enzyme responsible for synthesizing and maintaining the telomeres on the ends of chromosomes, and it is essential for cell proliferation. This has made hTERT a focus of oncology research and an attractive target for anticancer drug development. In this study, we designed a small interfering RNA (siRNA) targeting the catalytic subunit of ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- International journal of oncology
دوره 45 3 شماره
صفحات -
تاریخ انتشار 2014