Samaneh Hossainzadeh; Alireza Nouhi Kararoudi; Seyed Milad Mousavi Eshkelani; Safura Pakizehkar; Alireza Naderi Sohi; Farhood Najafi; Najmeh Ranji
Volume 25, Issue 4 , 2023
Abstract
Background: Colorectal Cancer (CRC) is the most common malignant gastrointestinal cancer. Cancer stem cells (CSCs) are the major cause of cancer recurrence and cancer drug resistance. Silibinin, as an herbal compound, has anticancer properties.
Objectives: The present study aimed to evaluate the antiproliferative ...
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Background: Colorectal Cancer (CRC) is the most common malignant gastrointestinal cancer. Cancer stem cells (CSCs) are the major cause of cancer recurrence and cancer drug resistance. Silibinin, as an herbal compound, has anticancer properties.
Objectives: The present study aimed to evaluate the antiproliferative effects of silibinin on HT29 stem-like cells (spheroids).
Methods: In this study, antiproliferative and apoptotic properties of Silibinin encapsulated in Polymersome Nanoparticles (SPNs) were evaluated by MTT assay, propidium iodide (PI) /AnnexinV assay, cell cycle analysis, and DAPI (4',6-diamidino-2-phenylindole) staining. The expression of some miRNAs and their potential targets was evaluated by real-time reverse transcription-polymerase chain reaction (qRT-PCR).
Results: IC50 of SPNs was determined at 28.13±0.78µg/ml after 24 h. SPNs (28µg/ml) induced apoptosis by 32.36% in HT29 cells after 24 h. DAPI staining indicated a decrease in stained nuclei after SPNs induction. SPNs treatment increased the expression of miR-34a, as well as P53, BAX, CASP9, CASP3, and CASP8. The downregulation of miR-221 and miR-222 was observed in SPNs treated cells. Moreover, SPNs decrease the expression level of CD markers in HT29 spheroids (cancer stem cells) compared to untreated spheroids. Spheroids were completely destroyed after 72 h treatment with SPNs (28µg/ml).
Conclusion: As evidenced by the obtained results, SPNs can be used as an effective anticancer agent in multi-layer (cancer stem cells) and mono-layer cancerous cells with the upregulation of tumor suppressive miRs and genes, as well as downregulation of oncomiRs and oncogenes.
Andia Seyedi Moghaddam; Mahdieh Salimi; Najmeh Ranji; Hossein Mozdarani
Volume 23, Issue 10 , 2021
Abstract
Background: The miRNAs are referred to small non-coding RNAs (consisting of 18 to 25 nucleotides). Functional studies have shown their functions to be oncogenes or tumor suppressor genes in different types of cancers. The miR-106b and miR-21 have been identified to participate in the biological behaviors ...
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Background: The miRNAs are referred to small non-coding RNAs (consisting of 18 to 25 nucleotides). Functional studies have shown their functions to be oncogenes or tumor suppressor genes in different types of cancers. The miR-106b and miR-21 have been identified to participate in the biological behaviors of cells.
Objectives: This study aimed to evaluate the tissue and plasma levels of miR-21 and miR-106b in patients with breast cancer who were diagnosed with ductal carcinoma.
Methods: In total, 40 cases of breast cancer patients 180 samples were examined in this project. Samples included ductal carcinoma breast tumors (n=40), normal breast tissues of the margin of the tumor (n=40) and 20 samples from unaffected mammary tissue of females undergoing reduction mammoplasty (control group), plasma samples of patients with breast cancer (n=40), and plasma of non-affected individuals (n=40). The expression levels of miR-106b and miR-21 were determined using SYBR Green real-time RT-PCR assay in breast tissues and plasma of cancerous patients in comparison to the controls.
Results: MiR-106b and miR-21 revealed much higher expression in tissues and plasma of patients with breast cancer in comparison to that in the group of control (P<0.001). High levels of mir-106b and miR-21 expression in plasma and tumor tissues were highly correlated with tumors in higher stages and lymph node involvement (P<0.0001).
Conclusion: Based on the obtained results, upregulation of miR-106b and miR-21 in the plasma of patients with breast cancer can act as a possible non-invasive biomarker for breast cancer prognosis. Further follow-up studies are required to confirm this.
Fatemeh Asadi Rahmani; Najmeh Ranji; Hamid Saeidi Saedi
Volume 23, Issue 6 , 2021
Abstract
Background: Gastric cancer (GC) is the most prevalent malignancy worldwide and a common cause of death in Iran. Studies have proved that a variety of dysregulated microRNAs is involved in the development and progression of gastric cancer.
Objectives: The present study aimed to evaluate the expression ...
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Background: Gastric cancer (GC) is the most prevalent malignancy worldwide and a common cause of death in Iran. Studies have proved that a variety of dysregulated microRNAs is involved in the development and progression of gastric cancer.
Objectives: The present study aimed to evaluate the expression levels of plasma circulating oncogenic miR-21 and miR-192 and their association with clinical phenotypes of patients with gastric cancer in the north of Iran.
Methods: Clinico-pathological analysis was conducted using a standard protocol and pathological tests. The expression levels of miR-21 and miR-192 were measured using quantitative reverse transcription-polymerase chain reaction in the plasma of twenty pre/post-operative gastric cancer patients and twenty healthy subjects. The receiver operating characteristic (ROC) curve of these microRNAs was analyzed to investigate their diagnosis properties.
Results: The study results indicated that plasma miR-21 expression was significantly associated with tumor stage and helicobacter pylori infection status (P=0.024, P=0.0004, respectively). However, no association was observed between clinic-pathological characteristics and miR-192 expression. The results showed that the plasma levels of miR-21 (P=0.0001) and miR-192 (P=0.0007) were significantly higher in GC patients compared to those in healthy individuals. Furthermore, the ROC analyses yielded the mean ±SD area under the curve (AUC) values of 0.9525±0.03 (P<0.0001) and 0.5925±0.09 (P=0.316) for miR-21 and miR-192, respectively. Pearson regression analysis showed that there was no significant correlation between the expression of miR-21 and miR-192 (P=0.1507).
Conclusion: Based on the obtained results, the expression of the plasma level of miR-21 was significantly higher in gastric cancer patients compared to that in the healthy group. Furthermore, the higher levels of AUC in miR-21 indicated the potential role of miR-21 as a noninvasive biomarker for the prognosis of gastric cancer in the population of the north of Iran.
Tolou Babaei Hemmaty; Najmeh Ranji; Fatemeh Safari
Volume 23, Issue 3 , 2021
Abstract
Background and Aims: Gastric cancer (GC) is a global health problem and the second deadly type of cancer worldwide with 1000 deaths per year. Poor prognosis in the early stages is one of the burdens in the treatment of GC. MicroRNAs are 18-22 nucleotide non-coding RNAs which play critical roles ...
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Background and Aims: Gastric cancer (GC) is a global health problem and the second deadly type of cancer worldwide with 1000 deaths per year. Poor prognosis in the early stages is one of the burdens in the treatment of GC. MicroRNAs are 18-22 nucleotide non-coding RNAs which play critical roles in the regulation of gene expression. Nowadays, miRNAs are widely known as non-invasive biomarkers for various kinds of cancers. This study aimed to evaluate the expression level of circulating miR-16 and miR-26a in GC patients and investigate the potential prognostic role of these miRNAs.
Material and Methods: Initially, 20 plasma samples were obtained from pre-and post-operative GC patients, and the expression of miR-16 and -26a were compared with that of 20 healthy controls. The miRNAs expression was investigated using Real-Time quantitative PCR. The association between the expression levels of these miRNAs and clinicopathological features was also investigated in this study.
Results: MiR-16 was down-regulated in GC patients; however, miR-26a expression revealed no significant difference between patients and controls in this regard. Furthermore, the expression of two miRNAs showed no association with the grade, TNM stage, and smoking status of the patients. Eventually, decreased expression of miR-16 was not correlated with the expression level of miR-26a.
Conclusion: The downregulation of circulating miR-16 introduces this microRNA as a candidate biomarker for the non-invasive early prognosis of GC.
Armaghan Shirinsokhan; Zeinab Khazaei Koohpar; Najmeh Ranji; Fatemeh safari
Volume 22, Issue 11 , 2020
Abstract
Background: Cadmium (Cd) is a natural and heavy metal, which is widely widespread in the atmosphere. Studies report that environmental exposure to Cd increases the risk of various disorders, such as pulmonary diseases. On the other hand, Cd increases the reactive oxygen species (ROS), which interacts ...
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Background: Cadmium (Cd) is a natural and heavy metal, which is widely widespread in the atmosphere. Studies report that environmental exposure to Cd increases the risk of various disorders, such as pulmonary diseases. On the other hand, Cd increases the reactive oxygen species (ROS), which interacts with biomolecules (e.g. DNA, proteins, and lipids) and causes severe damages. In addition, Cd may play a role in the dysregulation of the expression and activity of matrix metalloproteinases (MMPs). Since ROS and oxidative stress are likely the main reasons for MMPs dysregulation, antioxidants therapy may protect tissues against Cd-induced damages. Furthermore, N-acetylcysteine (NAC) protects cells against oxidative stress and toxic compounds.
Objectives: This study aimed to investigate the effect of cadmium (Cd) on the matrix metalloproteinases (MMPs) -2 and -9 expression in the lung, and the role of N-acetylcysteine (NAC) in preserving the lung cells against Cd toxicity.
Methods: The rats were randomly divided into five groups of G1 (control), G2 (single dose of Cd), G3 (continuous dose of Cd), G4 (single dose of Cd+NAC), and G5 (continuous dose of Cd+NAC). The level of Cd in the blood and lung tissue was measured by atomic absorption spectroscopy. Moreover, the expression of MMP2 and MMP9 genes was evaluated using RT-PCR.
Results: Single and continuous exposure to Cd caused a significant increase in serum and the lung tissue of Cd in G2 (0.23±0.04 mg/L and 0.35±0.047 ?g/g tissue) and G3 (0.50±0.068 mg/L and 0.81±0.063 ?g/g tissue) groups, compared to other groups (P<0.001). The NAC supplementation significantly decreased Cd levels in the serum and lung tissue samples of rats exposed to single or continuous Cd (P<0.001). Furthermore, exposure to a single and continuous dose of Cd caused a significant increase in the MMP2 expression by 3.24-fold (P=0.003) and 11.9-fold (P<0.001), respectively. Additionally, treatment with single and continuous dose treatment of Cd led to a significant increase in the MMP9 expression by 3.20-fold (P=0.004) and 7.54-fold (P<0.001), respectively. The NAC treatments decreased the expression of MMP2 and MMP9 in the lung of rats exposed to a single or continuous dose of Cd.
Conclusion: The Cd exposure was strongly associated with the accumulation of Cd and overexpression of MMP2 and MMP9 in the lung tissue. Moreover, the NAC can protect the lungs against Cd toxicity by decreasing Cd and down-regulating MMPs.
