It also plays an important role on the malignant tumor metastasis. The proliferation of host tumor cell is usually accompanied by simultaneous cancer cells migration that enable them to reach the target tissue [18]. During malignant tumor proliferation, the neoplastic cells firstly attach to the underlying basement membrane. After being degraded by proteases produced by malignant cells, tumor cells pass through the basement membrane, spread into adjacent
connective tissue. They proliferate ABT-199 molecular weight to form a metastasis in target tissue and induce angiogenesis [2]. MMP1 (collagenase-1), located on chromosome 11q22, is an important member of the MMP family that specifically degrades a major component of the ECM, type I collagen, as well as other fibrillar collagens of types II, III, V, and IX [13] and [32]. The MMP1 gene is expressed in
various kinds of normal cells, often at low levels under physiological conditions. However, MMP1 gene expression increases dramatically in a large number of malignancies, including head and neck cancer [25]. It is worth to mention that MMP1 is very important to metastasis and invasion of tumor cells because of its capability of degrading fibrillar collagen type Selleck Enzalutamide I and III [26], which consequently breaks the ECM molecules. RNA interference (RNAi) is a phenomenon of sequence-specific post-transcriptional gene silencing (PTGS) that is a conserved biological response. It was first discovered by plant biologists in 1980, but its molecular mechanism kept unknown until the late 1990. Andrew Fire and Ceaig Mell studied the nematode, Caenorhabditiselegans, and found that it is a specific silencing of genes, highly homologous in sequence to the delivered double-stranded RNA (dsRNA) [6]. This kind of process was considered to be a defense Carnitine palmitoyltransferase II mechanism against viral pathogens or uncontrolled transposon mobilization [19] and [31]. The mechanism of RNAi essentially
involves the effectors, short (21–28 nucleotides) dsRNA, and then degrades the target mRNA. RNAi is mediated by siRNAs that are processed from long dsRNAs of exogenous or endogenous origin by a cytoplasmic ribonuclease-III type called dicer [21]. The resulting siRNAs are about 21–23 nucleotides (nt) long and then incorporated into nuclease complex, a RNA-inducing silencing complex (RISC). The antisense strand of siRNA serves as a template for RISC to recognize, then targets and cleaves the mRNA containing a sequence identical to that of the siRNA, which can consequently then rapidly degrade mRNA [29]. In this study, 3 small double strand siRNAs (506-MMP1, 859-MMP1 and 891-MMP1), each contains 25–26 nucleotides, with 30–50% of GC content and high specific to human MMP1 were designed and synthesized according to mRNA sequence of human MMP1 (NCBI, NM_002421) and factors affecting RNA interfering efficiency from previous studies [1], [27], [12], [14] and [20].
Related posts:
- The Wnt signalling pathway plays a fundamental role in intestinal
- utations from the Smad4 gene in other tumor types are much less r
- Role of IFN ? in orlistat triggered inhibition of FASN expression
- CTCs represent tumor cells that have left the primary tumor and a
- The review also shows that TPX2 plays a crucial function in the p