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Background Breast cancer has a high prevalence among women worldwide. Tumor invasion and metastasis still remains an open issue that causes most of the therapeutic failures and remains the prime cause of patient mortality. Hence, there is an unmet need to develop the most effective therapeutic approach with the lowest side effects and highest cytotoxicity that will effectively arrest or eradicate metastasis. Methods An MTT assay and scratch test were used to assess the cytotoxicity and migration effects of Urtica dioica on the breast cancer cells. The QRT-PCR was used to study the expression levels of miR-21 , MMP1 , MMP9 , MMP13 , CXCR4 , vimentin , and E-cadherin . Results The results of gene expression in tumoral groups confirmed the overexpression of miR-21 , MMP1 , MMP9 , MMP13 , vimentin, and CXCR4 , and the lower expression of E-cadherin compared to control groups (P < 0.05). Moreover, the results of the MTT assay show that Urtica dioica significantly inhibited breast cancer cell proliferation. Moreover, findings from the scratch assay exhibited the inhibitory effects of Urtica dioica on the migration of breast cancer cell lines. Conclusion Urtica dioica extract could inhibit cancer cell migration by regulating miR-21 , MMP1 , MMP9 , MMP13 , vimentin , CXCR4 , and E-Cadherin . Moreover, our findings demonstrated that the extract could decrease miR-21 expression, which substantially lessens the overexpressed MMP1 , MMP9 , MMP13 , vimentin , and CXCR4 and increases E-cadherin in the tumoral group. [ABSTRACT FROM AUTHOR]

MicroRNAs’ expression profiles have recently gained major attention as far as cancer research is concerned. MicroRNAs are able to inhibit target gene expression via binding to the 3′ UTR of target mRNA, resulting in target mRNA cleavage or translation inhibition. MicroRNAs play significant parts in a myriad of biological processes; studies have proven, on the other hand, that aberrant microRNA expression is, more often than not, associated with the growth and progression of cancers. MicroRNAs could act as oncogenes (oncomir) or tumor suppressors and can also be utilized as biomarkers for diagnosis, prognosis, and cancer therapy. Recent studies have shown that such herbal extracts as Shikonin, Sinomenium acutum, curcumin, Olea europaea, ginseng, and Coptidis Rhizoma could alter microRNA expression profiles through inhibiting cancer cell development, activating the apoptosis pathway, or increasing the efficacy of conventional cancer therapeutics. Such findings patently suggest that the novel specific targeting of microRNAs by herbal extracts could complete the restriction of tumors by killing the cancerous cells so as to recover survival results in patients diagnosed with malignancies. In this review, we summarized the current research about microRNA biogenesis, microRNAs in cancer, herbal compounds with anti-cancer effects and novel strategies for employing herbal extracts in order to target microRNAs for a better treatment of patients diagnosed with cancer. [ABSTRACT FROM AUTHOR]

Introduction Medical plants have been intensively studied as a source of antitumor compounds. In the present study, we determine the effect of Scrophularia oxysepala on triggering apoptosis and diminishing growth, size and weight of the tumor in the allograft model of Balb/c mice. Material & methods The cytotoxic effects of Scrophularia oxysepala extract on 4T1 cells were studied using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) assay and Trypan blue staining. DNA fragmentation assay was done for apoptosis detection. After the establishment of tumor in Balb/c mice, two groups of mice were received the extract at two doses of 50 and 100 mg/kg respectively using intraperitoneal injection once every two days for 28 days. In order to assess the induction of apoptosis in cancer cells, the TUNEL assay was carried out in tumoral tissues. Moreover, the Ki67 test was used to evaluate tumor proliferation. Results According to the findings, the Scrophularia oxysepala extract inhibited cell growth. In vivo results showed that tumor size in mice treated with the extract was significantly reduced. The weight of tumor mass in treated mice after resection was less than the control group. According to the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay results, the herbal extract induced apoptosis in tumoral cells. Ki67 test also demonstrated that administration of the extract suppressed the growth of tumor cells. Conclusion Our data well approved the anti-proliferative effect of Scrophularia oxysepala extract, and clearly showed that, the plant extract can decrease the growth of breast cancer cells in tumor mass. Thus it may represent an ideal therapeutic tool for breast cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is still the third most common cancer in the world. Mechanism of CRC tumorigenesis has been widely studied at the molecular levels, and has been recently entered the area of microRNAs. MicroRNAs are small 19 to 22 nucleotides of RNA that engage in the regulation of cell differentiation, apoptosis, and cell cycle progression. MicroRNAs are similar to small interfering RNA (siRNA), that post-transcriptionally regulate gene expression and control various cellular mechanisms. They are important factors in the carcinogenesis of CRC, one of the most important factors includes microRNA. MicroRNAs have been linked to CRC development, and these molecules have been recently studied as new potential biomarkers in diagnosis and treatment of CRC. Specific microRNA expression patterns help distinguish CRC from other colon related disease, and may be used as a prognostication factor in patients after treatment with different chemotherapy drugs. More over the newest molecular therapy via tumor suppressor micro RNA replacement can be new insight in molecular therapy of CRC. This review summarizes the potential roles of microRNAs as potential biomarkers for CRC diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Introduction Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line. Materials and methods To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry. Results Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1. Conclusions Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel. [ABSTRACT FROM AUTHOR]

Abstract MicroRNAs are post-transcriptional mediators of gene expression and regulation, which play influential roles in tumorigenesis and cancer metastasis. The expression of tumor suppressor miR-145 is reduced in various cancer cell lines, containing both solid tumors and blood malignancies. However, the responsible mechanisms of its down-regulation are a complicated network. miR-145 is potentially able to inhbit tumor cell metastasis by targeting of multiple oncogenes, including MUC1, FSCN1, Vimentin, Cadherin, Fibronectin, Metadherin, GOLM1, ARF6, SMAD3, MMP11, Snail1, ZEB1/2, HIF-1α and Rock-1. This distinctive role of miR-145 in the regulation of metastasis-related gene expression may introduce miR-145 as an ideal candidate for controlling of cancer metastasis by miRNA replacement therapy. The present review aims to discuss the current understanding of the different aspects of molecular mechanisms of miR-145 regulation as well as its role in r metastasis regulation. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the most prevalent cancers with high mortality in the world. MicroRNAs are a class of small non-coding RNAs that regulate gene expression through targeting mRNAs. MicroRNAs involve in many biological and pathological processes such as cell growth, differentiation, apoptosis. etc. Dysregulation of miRNAs expression patterns have been reported in many tumors including Colorectal Cancer. Various studies indicate that miRNAs can be utilized as diagnostic and prognostic biomarkers for evaluation of tumor initiation, development, invasion, metastasis and response to chemotherapeutic drugs. Numerous investigations have also shown dysregulation of miRNAs in tissue samples and body fluids such as serum, plasma and fecal samples from CRC patients. Recently, several studies have demonstrated that miRNAs have regulatory roles in response to anti-cancer drugs and suggested them as predictive factors for successful treatment. In this review, we highlight the facts concerning tumor suppressor miRNAs and oncomiRs in CRC; by emphasizing their importance in different signaling pathways such as the Wnt/β catenin activation, EGFR pathway, (TGF-ß) and the TP53 network and then their potential as biomarker and targets for cancer treatment. [ABSTRACT FROM AUTHOR]

Background Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer. Methods Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had survival effects on EJ-138 cells. Scratch wound healing assay measured cell motility effects after snail1 suppression. Results The significant silencing of snail-1 reached 60 pmol siRNA in a 48-h post-transfection. The result of scratch assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and CXCR4 expression; however, expression of E-cadherin was induced. The cell death assay indicated that snail-1 played the crucial role in bladder cancer survival rate. Conclusion These results propose that snail-1 plays a major role in the progression and migration of urinary bladder cancer, and can be a potential therapeutic target for target therapy of invasive urinary bladder cancer. [ABSTRACT FROM AUTHOR]

Gastric cancer is responsible for approximately one million annual deaths worldwide. Recently, the important roles of miRNAs as vital factors in malignancy processes such as metastasis have identified. They involve in the regulation of different biological procedures such as proliferation, invasion, metastasis and cell survival. MiR-146a has an aberrant expression in different tumors and has different expressions in the gastric cancer cell lines. This microRNA can act as a tumor suppressor and/or oncogene in gastric cancer related cases. Most of the studies have confirmed that miR-146a is downregulated in human gastric cancer cell lines and tissues, significantly and that it has tumor suppressor effects in gastric cancers. On the other hand, the role of miR-146a as an oncogene has been studied in an in-vitro experiment and results showed that over- an expression of miR-146a in gastric cancer tissues inhibits apoptosis and improves cell proliferation of gastric cancer cell. MiR-146a also has been a candidate for diagnosis and prognosis in gastric cancer cases. In this review, we focus on the important roles of miR-146a in tumor genesis of gastric tissues, emphasizing on the involvement of this microRNA in diagnosis, prognosis, chemotherapy response and finally, potential therapeutic applications as an anticancer agent in inhibition of gastric cancer cell metastasis and invasion. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome. MiRNA-143 is defined as an important tumor suppressor in a variety of neoplasms including solid tumors and B-cell malignancies. MiRNA-143 is involved in the pathogenesis of cancers by directly targeting several mRNAs such as Bcl-2 , KRAS , HK2 , DNMT3A , TP53 and MMP-13 . In this study, an overview of the miRNA-143 function in different signaling pathways in cancer will be provided. [ABSTRACT FROM AUTHOR]

Background Despite the great improvements in clinical and therapeutic techniques in recent years, many advanced breast cancer patients still died of the postoperative recurrence and metastasis of disease. Bach1 plays a role in the development of the invasive phenotypes of cancer, cell division and apoptosis in tumor cells. The aim of this study was to investigate the effect of specific bach1 siRNAs, on the proliferation, migration, invasive, induction of apoptosis, cell cycle arrest and alter EMT related miRNA of MDA-MB-468 cells (breast cancer). Methods siRNA transfection was performed with transfection reagent. The expression levels of Bach1 mRNA and protein were measured by qRT-PCR and western blot analysis, respectively. The survival of cells was determined using MTT assay cells, apoptosis using Tunel assay, Cell migration using scratch assay and Cell cycle analysis by Propidium Iodide (PI) DNA staining method by using flow cytometry on the MDA-MB-468. The expression levels of MMP-9 and CXCR4 were measured by qRT-PCR. Results Transfection with siRNA significantly suppressed the expression of bach1 gene in dose dependent manner after 48 h ( p < 0.0001). Surprisingly, treatment with bach1 siRNA arrest cell cycle in S phases ( p < 0.0001). Moreover siRNA transfection had effects on breast adenocarcinoma cells and inhibits the migration ( p < 0.0001), proliferation ( p < 0.0001), cell cycle arrest ( p = 0.03) and induces apoptosis ( p < 0.0001) and reduces the expression of miR-21 ( P = 0.0014). Conclusion Our results suggest that the bach1 can be considered as a potent adjuvant in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486–5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486–5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486–5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486–5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24-CD44+ cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486–5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486–5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is considered one of the leading types of cancer in the world. CD133, as a cancer stem cell marker, has a pivotal role in the development of drug resistance, migration, and stemness properties of CRC cells. This study was designed to check the combined effect of CD133 siRNA and Oxaliplatin on proliferation, migration, apoptosis, and stemness properties of CRC cells in the HT-29 cell line. MTT assay was performed to define the combined effect of CD133 siRNA and Oxaliplatin on the viability of HT-29 cells, and it showed that the combination of CD133 siRNA and Oxaliplatin could reduce the IC50 of this drug from 32.85 to 19.75 nmol. In order to figure out the effect of this combination therapy on CD133 expression at the gene and protein level, qRT-PCR and western blot were exploited, respectively. The results demonstrated that the silencing of CD133 could reduce the relative expression of this marker to about 0.00001 compared to the control group and reduce the protein level to 0.01. The ability of cell migration was tested by wound healing assay as well. Also, colony formation and sphere formation were conducted to assess the stemness properties in the combination group. Flow cytometry was conducted to investigate the apoptosis (15%), cell cycle (about 10% arresting in G0-G1 phase), and surface expression of CD133 in different groups (from 39.3% in the control group to 2.41 in the combination group). Finally, the expression of migration-, and stemness-associated genes were measured by qRT-PCR. We indicated that silencing of CD133 reduces the migration and stemness properties of colorectal cancerous cells. This suppression makes HT-29 cells more sensitive to Oxaliplatin and reduces the effective dose of this chemical drug. Therefore, the suppression of CD133 in combination with Oxaliplatin treatment might be a promising therapeutic approach in the treatment of colorectal cancer. [Display omitted] • Silencing of CD133 makes HT-29 cells more sensitive to Oxaliplatin. • Silencing of CD133 reduces migration and stemness properties. • CD133 silencing decreases metastasis and stemness related genes expression. • CD133 silencing in combination with Oxaliplatin induces apoptosis. [ABSTRACT FROM AUTHOR]

Abstract Background Lung cancer is the main cause of cancer death in males and females worldwide. Reduced expression of miR-145 has been reported in many types of cancers. In this study, we transfected miR-145 into lung cancer cells by vector-based miR-145, and investigated the effects of this intervention on growth and migration inhibition of cancer cells as well on the expression of targeted genes. Methods IC50 of Geneticin (G418) antibiotic was measured using MTT test in NSCLC cell lines. miR-145 was transfected into lung cancer cells by jetPEI. qRT-PCR was used to evaluate the transcript level of the miR-145 and expression for KRAS , MMP-9 , vimentin, caspase-3 , caspase-8 and caspase-9 genes in A549 cells. MTT assay was used to evaluate the proliferation inhibition of cancer cells. Wound healing assay was used to check the migration status of transfected lung cancer cells. The apoptosis induction was assessed by DAPI staining assay. Results The MTT assay showed that the IC50 of Genticin was 494.1 μg/ml. The results of the qRT-PCR showed increased expression level of miR-145 and downregulation of KRAS, MMP-9, and vimentin expression in A549 transfected cells compared with the control group. The MTT assay results demonstrated inhibition of cancer cell proliferation after miR-145 replacement. Wound healing assay results revealed that migration was reduced upon miR-145 transfection. The transfected cell displayed increased apoptosis rate by inducing caspase-3 and caspase-9 mRNA expression. Conclusion The results of this study showed that increased miR-145 expression exerted a critical role in subsiding the growth, survival, and migration of lung cancer cell line. [ABSTRACT FROM AUTHOR]

Introduction Breast adenocarcinoma is the second common cancer in women the incidence of which is increasing in many countries, especially in developing companies. In this study, miRNA143 has been replaced by vector based microRNA-143 in breast adenocarcinoma cells (MDA-MB-468) and its anti-cancer effects on breast adenocarcinoma cells have been evaluated. Methods The pCMV-MIR-143 vector was transfected into MDA-MB-468 cells via JetPEI transfection reagent. The transfected cells were selected by IC50 concentration of Geneticin antibiotic (G418) after a 2-week treatment. To evaluate the effect of miR-143 on the inhibition of migration, scratch wound healing assay was performed. Then, the expression level of miR-143, Kras, Vimentin, CXCR4, MMP9 and E-Cadherin were measured by the qRT-PCR method. Results Results of MTT and wound healing assays showed that miR-143 inhibited cell growth and cell migration in miR-143 induced cell line compared with control group. The result of gene expression showed that miR-143 reduced Kras, Vimentin, CXCR4 and MMP9 expression, and increased E-Cadherin expression in miR-143 replaced cells compared to control cells. Conclusion The results showed that miRNA-143 plays an important role in cell growth and migration during breast cancer development and metastasis and it can be a candidate as a therapeutic molecule in microRNA replacement therapy of breast adenocarcinoma. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay. Apoptosis was quantified using TUNEL assay and flow cytometry. Results showed that in Jurkat cells after transfection with PTPN22 siRNA, the expression of PTPN22 in both mRNA and protein levels was effectively reduced. Moreover, siRNA transfection induced apoptosis on the viability of T-cell acute leukemia cells. More importantly, PTPN22 positively regulated the anti-apoptotic AKT kinase, which provides a powerful survival signal to T-ALL cells as well as the suppression of PTPN22 down regulated ERK activity. Our results suggest that the PTPN22 specific siRNA effectively decreases the viability of T-cell acute leukemia cells, induces apoptosis in this cell line, and therefore could be considered as a potent adjuvant in T-ALL therapy. [ABSTRACT FROM AUTHOR]

Background Metastasis to distant organs is a hallmark of many tumor cells. BACH1 (BTB and CNC homology 1) is a transcriptional factor which promotes the migration and invasion of breast cancer cells. BACH1 expression and its target genes are intimately associated with the metastasis possibility of clinical samples, and BACH1 reduction leads to meaningful depletion in metastasis. The evaluation of BACH1 role in colon cancer remains elusive. This study seeks to further investigate the role of BACH1 in colon cancer cells. Methods Quantitative RT-PCR (qRT-PCR) was used to detect BACH1 expression and other related metastatic genes following siRNA knockdown in colon cancer HT-29 cells. And the protein level assessed by Western blot. MTT assay was to measure the changed cell viability after BACH1 siRNA transfection. Scratch-wound motility assays measured capacity of tumor cell migration of HT-29 cells after BACH1 silencing. Results The inhibitory effect of BACH1 was performed by siRNA knockdown using highly metastatic HT-29 colon cell lines. Quantitative RT-PCR and Western blot analysis revealed that the expression levels of BACH1 mRNA and protein in HT29 cells were significantly suppressed after transfection. Conversely, the BACH1 expression increased migration. Also the CXCR4 and MMP1 expression levels decreased following BACH1 knockdown in HT-29 cells. Conclusion Our results indicated that BACH1 down-regulation in HT29 CRC cells had no effect on cell growth but did inhibit cell migration by decreasing metastasis-related genes expression. Collectively, these results suggest that BACH1 may function as an oncogenic driver in colon cancer and may represent as a potential target of gene therapy for CRC treatment. [ABSTRACT FROM AUTHOR]