Lab Report

Non-small cell lung cancer (NSCLC) represents 85% of lung cancer case1,2. Due to metastasis and other individual conditions, only 30% of the patients are able to go for a surgery, the best regarded treatment method2. Others predominately use tradition chemo- and radio-based therapeutic methods, which held poor treatment outcome with only 15% of the patient lives longer than 5 years1. However, since the establishment of RNAi therapy in 1998, the efficacy of RNAi on tumour activity related genes was intensively studied and some research trials has shown potential effects in treating NSCLC by this method1-3.

Breast cancer is the second most common cancer in women worldwide. The most common type of breast cancer is ductal carcinoma, which arises in cells that lines breast duct. Many imaging techniques are used for the screening and diagnosis, but typically patients are diagnosed at advanced stage only, and the prognosis is associated with early detection. At present serum and protein biomarkers improving early detection of breast cancer, these make better treatment options with a better response. MicroRNAs and CA 15-3 most widely used serum biomarker in breast cancer. Amplification of chromosomal regions encoding oncogenic miRNAs is consequently silencing or inhibits tumor suppressor genes. The standard treatment options for breast

We have also noticed, the absence of miR-4792, miR-4485-3p, miR-4532 and miR-486-5p in our Ago2-complex, compared to total cellular miRNA profile. No proper signal was detected, using NB. These miRNAs might be part of transfer RNA, or associated with other type of Ago protein, or could be a degraded tRNA product. The function of aforementioned potential miRNAs should be investigated in more details. Mir-221-3p and miR-155-5p were induced in U2932-EBV cells, compared to U2932 cell line. These results were consistent with Lawrie et al. data [137]. Mir-221-3p was not detected in neither of SUDHL5-EBV or SUDHL5 cell line.

Hepatocellular carcinoma (HCC), a lethal liver cancer, has a very poor prognosis and is in dire need of novel targets to develop more effective treatments. The conventional treatment options of surgery and chemotherapy were limited to pre-metastatic HCC; however, a multi-kinase inhibitor, in addition to targeting other factors involved in development and progression of the disease showed promising results in advanced HCC [42]. LncRNAs such as HOTAIR, MALAT1, and H10 are dysregulated and have been suggested to play an essential role in HCC development whereas dysregulation affects proliferation, apoptosis, and metastasis. This is also true for gastric cancer, whereby dysregulation of lncRNAs- HOTAIR, HULC, and H19 are relatively linked to development, metastasis, and prognosis [43]. HCC is also characterized by aberrant expression of miRNAs. Respectively, upregulation and downregulation has been associated with invasion and metastasis, tumor progression, and drug resistance. Meng et al. proposed that aberrantly expressed miRNAs may regulate the expression of certain genes that control cell growth, migration, and invasion. In this study, the expression of miRNA in normal versus tumor tissue was investigated which led to the identification of overexpressed miR-21 in human HCC that could potentially serve as a target for regulating downstream events [44].

The general characteristics of tumor include the increased proliferation rate and migration ability, the loss of cellular identity and the failure of controlling the cellular death. How is miRNA involved in the development of cancer? Kolokythas et al. considered it was possible that the involvement of miRNA in cancer merely reflected the loss of normal cellular characteristics during malignant transformation [21]. Furthermore, microRNAs have also been documented to have roles in all of the cancer hallmarks defined by Hanahan and Weinberg in 2011[18-13].

Just after the Valadi’s discovery in 2007(59), various studies have been performed, in order to characterize exosomal miRNA as diagnostic biomarkers for cancers. In 2008, Taylor et al. reported that eight miRNAs, including miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205 and miR-214, previously demonstrated as diagnostic markers for ovarian cancer, were also present in serum exosomes, isolated from the ovarian cancer patients (74). In 2009, Rabinowits and collegues carried out a miRNA-profiling analysis on tumor biopsy specimen, exosomes isolated from lung adenocarcinoma patients and control subjects. They found a similar miRNA profile between exosomes and tumor biopsy samples from

DKK1 interfere with canonical WNT activity by binding to LRP5/6. Studies have shown that loss of membrane expression of β-catenin may be significantly associated with poor prognosis and considered a biomarker for OSCC recurrence (Aguiar et al, 2007; Mahomed et al. 2007). p53 is a known tumour suppressor gene. Activation of the Wnt pathway and loss of p53 are frequently known mechanisms in cancer. However, the link between these two mechanisms has been studied by Kim et al in lung and breast cancer cells. Transactivation of miRNA 34 by p53, suppresses the trancriptional activity of β catenin -Tcf/Lef complexes. Loss of p53 increases the expression of endogenous β catenin, WNT1 and LRP6 thereby increasing canonical Wnt signaling (Kim et al,2011).

Therefore, it is worthy to notice such special expression difference of miR-193a-5p in lung cancer. The reasons causing such inverse peripheral blood and tissue miR-193a-5p expression remain unclear yet. It still needs additional larger samples studies to validate and provide exact explanation. Still, peripheral blood and tissue miR-193a-5p could provide a certain reference value for clinical lung cancer diagnosis.

Millions of people in the world know someone or have personally been afflicted with the disease that causes uncontrolled division of abnormal cells in a part of the body, better known as cancer. In the US alone half of all men and one third of all women will develop cancer at some point in their life. There are over 100 known cancers and they all, even when treated or caught early can lead to serious illness and death. This is why researchers and doctors everywhere are looking for answers to cure these diseases and stop cancer in its tracks. Many cancers have been analyzed and great steps of progress have been made into cancer prevention, spotting the development of cancer cells early, and finding treatments to cure people who have been affected with the disease. One topic scientist have taken particular interest in is the miR-200 family and its role in tumor angiogenesis regulation. In a paper written by Pecot et al (2013), Tumor angiogenesis regulation by the miR-200 family, scientist investigated the miR-200 family's role in inhibiting the epithelial-mesenchymal transition, which suggests it inhibits metastasis. The researchers hypothesized through direct and indirect mechanisms, the miR-200 family will show angiogenesis inhibition by regulating interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. This review will delve into the mir-200 family members, methods used by the researchers, and results that were obtained.

Gastrointestinal (GI) cancers, such as colon and pancreas are highly resistant to both standard and targeted therapeutics. Therapy-resistant and heterogeneous GI cancers harbor highly complex signaling networks (Resistome) that resist apoptotic programming. Commonly used Gemcitabine (GEM) or platinum-based regimens fails to induce perturbations in the resistome, resulting in high rate of treatment failure. GI cancer resistance networks are in part due to interactions between parallel signaling and aberrantly expressed microRNAs (miRNAs) that collectively promote the development and survival of drug-resistant cancer stem cells (CSCs) with epithelial-to-mesenchymal transition (EMT) characteristics. The lack of understanding of

It has been reported in lung cancer tissues and cell line MIRL lncRNA acts as an oncogene. This downregulation is confirmed by knocking down MIR4435-2HG in lung cancer and treating the lung cancer cells with resveratrol. In both the cases,

In breast cancer researchs it is have appeared that CSCs in this type of cancer are resistant to chemotherapy, radiotherapy, and hypoxia. Furthermore, the high tumorigenicity and invasiveness of CSCs are crucial to the occurrence, development, metastasis, and recurrence of breast cancer . Different LncRNAs including, HOTAIR , LncRNA ROR, LncRNA 00617, LncRNA SOX2OT and LncRNA-Hh have been showed that affect the characteristics of breast CSCs by influencing the Epithelial mesenchymal transition (EMT) -related signaling pathways [15, 16, 34-36].

Since the discovery of miRNA by Victor Ambros, the function of miRNAs in developmental timing in C. elegans, was extended to the association of miRNAs with cancer. We now know that miRNAs can act as oncogenes (oncomiRs), by inducing different mechanism such as cell proliferation, migration and invasion, tumor growth and metastasis, or act as a tumor suppressors by inhibiting cell proliferation, migration and invasion [52]. The most common molecular genetic changes in miRNA expression level or genetic abnormality, which will be discussed below have been found to be linked to numerous cancers as follows:

MicroRNA-145 (miR-145) expression shows an inhibitory effect on the proliferation of human cancer cells. In HCC, the expression of miR-145 was found to be significantly downregulated as a result of HBx interaction. Gao et al. identified Cullin-5 (CUL5) as a target of miR-145. CUL5 has been reported to be functionally involved in numerous cellular activities including the cell cycle. In addition, CUL5 was also reported to be involved in regulating apoptosis by modulating the phosphorylation of mitogen-activated protein kinase (MAPK) and induce p53 mRNA and protein expression. The substantial increase in the expression of CUL5, due to the inhibition of a miRNA-145 expression by HBx, results in less phosphorylation of MAPK and therefore less p53 mRNA and protein expression. This study confirmed a significant decrease in the expression of miRNA-145 and a substantial increase in the mRNA and protein expression of CUL5 in HBx-over-expressing cells compared with empty vector-transfected cells. The proliferation of the cells transfected with HBX plasmid markedly increased compared with cells transfected with empty vector.

MicroRNAs (miRNAs) comprise a large family, its having approximately 20–22 nucleotides, and it regulates the expression of target genes at the post-transcriptional level. However, thousands of miRNAs have been identified in many organisms (roundworms, flies, fish, frogs, mammals, flowering plants, mosses, and even viruses) by using genetics, molecular cloning and predictions from bioinformatics technique (Lagos et al., 2001; Lim et al., 2003; Pfeffer et al., 2004; Axtell and Bartel, 2005). The whole human genome encodes at least 474 miRNA genes (Griffiths, 2004; Griffiths et al., 2006), and in human breast cancer there are 133 miRNAs were identified. MiRNAs control messenger RNA expression and which are frequently dysregulated in