Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.
The upregulated expression of miR‑378a‑3p also increased the expression levels of B‑cell lymphoma 2‑associated X protein and caspase‑3, and decreased the expression levels of matrix metalloproteinase (MMP)‑2 and MMP‑9, which attenuated ESCC tumorigenesis.
Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis.
In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.
In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress) DNA damage-induced genomic instability and carcinogenesis.
These results highlight apoptosis-related CASP3 as an important gene in human carcinogenesis and further support the CASP3 polymorphisms confer to the lung cancer susceptibility.
ABHD5 deficiency provides CASP3 an advantage to cleave and inactivate BECN1, thus impairing BECN1-induced autophagic flux and augmenting genomic instability, which subsequently promotes tumorigenesis.
In addition, miR-320 induces apoptosis via down-regulation of Mcl-1 and activation of caspase-3 but inhibits cell proliferation, migration, invasion, and tumorigenesis in cervical cancer cells.
Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice.
We report that a central effector of apoptosis, caspase-3, facilitates rather than suppresses chemical- and radiation-induced genetic instability and carcinogenesis.
MiRNAs are characteristically expressed in tumor-initiating Sca-1(+) CD34(+) cells of lung adenocarcinoma, and may play important roles during the carcinogenesis of lung adenocarcinoma.
Moreover, miR-122-SP overexpression rescued the effects of ectopic miR-122 on suppressing proliferation, inhibiting cell migration and invasion, arresting cell cycle at G1 phase, and activating caspase-3/7, not only in Huh7 human hepatoma cells, but also in U2OS osteosarcoma cells. miR-122-SP also knocked down endogenous miR-122 expression in Huh7 and promoted tumorigenesis in vivo. miR-122-SP therefore is a useful tool that may be utilized to study the functions of miR-122 with regard to liver development and tumorigenesis in vitro and in vivo.
Given the biotoxicity of cadmium and its association with carcinogenesis, the effect of that metal ion (Cd(II)) was investigated, in a concentration-dependent fashion, on cell viability, cell proliferation, caspase-3 mediated apoptosis and H-ras gene expression in human breast cancer epithelial MCF-7 cells transfected with the H-ras oncogene (wild type and G12V mutation).
We found that B[a]P could cause oxidative stress damage, upregulate mitochondrial cytochrome-c and caspase-3 expression, induce lung carcinogenesis in female mice, E2 promoted these effects of B[a]P while tamoxifen (TAM) inhibited this effects of E2.
Unlike nontransformed epithelium lacking ERBB3, intestinal tumors lacking ERBB3 had reduced PI3K/AKT signaling, which led to attenuation of tumorigenesis via a tumor-specific increase in caspase-3-mediated apoptosis.
Caspase-3 plays a central role in executing cell apoptosis and thus in carcinogenesis, but little is known about the role of CASP3 variants in susceptibility to SCCHN.
Up-regulated expression of FasL and down-regulated expression of Caspase-3 in cancer cells of primary foci play an important role in gastric carcinogenesis.
Low expression of PTEN can decrease expression of Caspase-3 to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.
In addition, it was at the posttranscription level that the tumorigenesis of leiomyoma modulated the expressions of FasL and caspase 3 higher, whereas LA suppressed them at gene transcription.
Impaired function of apoptosis-related genes is deeply involved in oncogenesis and the progression of cancers, and caspase-3 plays a critical role as an executioner of apoptosis.