Papers by sara hajibabaei
Research Square (Research Square), Aug 3, 2023
Background: The MYC gene is one of the regulatory and proto-oncogenic genes overexpressed in most... more Background: The MYC gene is one of the regulatory and proto-oncogenic genes overexpressed in most prostate cancers (PCa). Studies have shown that abnormal expression of microRNAs is involved in the onset and development of many different types of human cancer, including prostate cancer. Methods and result: In this study, we rst evaluated targeting the effect of miR-377 on MYC by luciferase assay. Real-time PCR was used to determine whether miR-377 could decrease the MYC mRNA in transfected PCa cell lines (PC-3 and DU145). Also, the expression of BCL-2/Bax, PTEN, and CDK4 mRNA levels were measured due to MYC degression. Also, the effects of miR-377 on apoptosis cells, proliferation, cell cycle, and wound healing were analyzed. We showed that miR-377 targets MYC mRNA by luciferase reporter assay. A signi cant reduction in MYC mRNA level was detected following miR-377 transfection in PC-3 and DU145 cell lines. Also, we demonstrated the decrease of BCL-2 and CDK4 and an increase in Bax, and PTEN in prostate cancer cell lines, following the reduction of MYC. Furthermore, we showed that the higher levels of miR-377 in PCa cell lines induced apoptosis, reduced proliferation, and migration, and stopped the cell cycle. Conclusion: All these data reveal that miR-377 functions as an MYC inhibitor in PCa and may serve as a potential therapeutic target for treating this cancer.
Research Square (Research Square), Mar 1, 2023
The MYC gene is one of the regulatory and proto-oncogenic genes that is overexpressed in most pro... more The MYC gene is one of the regulatory and proto-oncogenic genes that is overexpressed in most prostate cancers. Studies have shown that abnormal expression of microRNAs is involved in the onset and development of many different types of human cancer, including prostate cancer. Materials and methods In this study, we rst evaluated targeting the effect of miR-377 on MYC by luciferase assay. Real-time PCR was used to gure out whether miR-377 could decrease the target gene mRNAs in transfected PCa cell lines (PC3 and DU145). The effects of miR-377 on apoptosis cells, proliferation, cell cycle, and wound healing were analyzed. Results We showed that miR-377 targets MYC mRNA by luciferase reporter assay. A signi cant reduction in MYC mRNA level was detected, following miR-377 transfection in PC3 and DU145 cell lines. The higher levels of miR-377 in PCa cell lines induced apoptosis, reduced proliferation, and migration, and stopped the cell cycle. Conclusion All these data reveal that miR-377 functions as a tumor suppressor in PCa and may serve as a potential therapeutic target for the treatment of this cancer.
فصلنامه بیماریهای پستان ایران, Feb 1, 2022
Introduction: PD-L1 is one of the most important immune control molecules in breast cancer and pl... more Introduction: PD-L1 is one of the most important immune control molecules in breast cancer and plays an important role in suppressing the immune system against tumor cells. Controlling the expression of PD-L1 at mRNA level using miRNA inhibitors could be helpful strategy for cancer treatment. In this study, considering the possible role of miR-145 as a tumor suppression in breast cancer, its involvement in reducing PD-L1 expression in breast cancer cell lines has been investigated. Methods: First, the targeting of miRNA-145 on 3 'UTR of PD-L1 gene was confirmed using bioinformatics software and then by luciferase dual reporter assay. The expression level of miRNA-145 was measured in breast cancer cell lines compared to normal line. After transfection of miRNA-145 into breast cancer cell lines, qRT-PCR was used to evaluate the effect of miRNA-145 on PD-L1 expression. Results: we showed that decreased expression of miRNA-145 in breast cancer cell lines was directly related to increased PD-L1 expression (r =-0.6175, P value₌0.0457). In addition, increased expression of miRNA-145 in breast cancer cell lines MDA-MB231, BT549 and MCF7 significantly reduced PD-L1 expression (1.938±0.212, 1.784±0.03 and 0.083±0.02 respectively). Conclusion: Our findings suggest that miRNA-145, by targeting the PD1/PD-L1 pathway and reducing PD-L1 expression, may be a therapeutic agent to prevent the progression of breast cancer.
Scientific Reports, May 27, 2023
Non-coding RNAs, including Inc-RNA and miRNA, have been reported to regulate gene expression and ... more Non-coding RNAs, including Inc-RNA and miRNA, have been reported to regulate gene expression and are associated with cancer progression. MicroRNA-561-3p (miR-561-3p), as a tumor suppressor, has been reported to play a role in preventing cancer cell progression, and MALAT1 (Lnc-RNA) have also been demonstrated to promote malignancy in various cancers, such as breast cancer (BC). In this study, we aimed to determine the correlation between miR-561-3p and MALAT1 and their roles in breast cancer progression. The expression of MALAT1, mir-561-3p, and topoisomerase alpha 2 (TOP2A) as a target of miR-561-3p was determined in BC clinical samples and cell lines via qRT-PCR. The binding site between MALAT1, miR-561-3p, and TOP2A was investigated by performing the dual luciferase reporter assay. MALAT1 was knocked down by siRNA, and cell proliferation, apoptotic assays, and cell cycle arrest were evaluated. MALAT1 and TOP2A were significantly upregulated, while mir-561-3p expression was downregulated in BC samples and cell lines. MALAT1 knockdown significantly increased miR-561-3p expression, which was meaningfully inverted by co-transfection with the miR 561-3p inhibitor. Furthermore, the knockdown of MALAT1 by siRNA inhibited proliferation, induced apoptosis, and arrested the cell cycle at the G1 phase in BC cells. Notably, the mechanistic investigation revealed that MALAT1 predominantly acted as a competing endogenous RNA in BC by regulating the miR-561-3p/TOP2A axis. Based on our results, MALAT1 upregulation in BC may function as a tumor promoter in BC via directly sponging miRNA 561-3p, and MALAT1 knockdown serves a vital antitumor role in BC cell progression through the miR-561-3p/TOP2A axis. Breast cancer is an urgent global priority. This disease is the most common cancer in women, accounting for 30% of newly reported cases, and is one of the leading causes of cancer deaths 1. BC is generated via one-of-a-kind elements like age, menarche history, reproductive patterns, bodily activity, breast traits, and physique habitus. Although tremendous advances have been made in the early detection and therapeutics of breast cancer over the last 20 years, the disease remains a significant public health problem 2. In this context, novel therapeutic techniques for BC are in pressing need. We undertook a long non-coding RNA (LncRNA)-based method to apprehend the underlying mechanism in BC development and enhance novel intervention strategies. LncRNA genes are a significant proportion of non-coding RNAs that play a vital role in normal growth and also in the tumorigenesis process 3. It is estimated that the human genome contains 23,000 LncRNA genes, which is more than 20,000 protein-coding genes 4. Their physiological and pathological functions are mediated by their interactions with microRNAs, mRNAs, proteins, and genomic DNA 5. Since the deregulation of gene expression
Scientific Reports, Jan 18, 2023
PD-L1 is one of the most important immune checkpoint molecules in breast cancer that plays an imp... more PD-L1 is one of the most important immune checkpoint molecules in breast cancer that plays an important role in suppressing the immune system when confronted with tumor cells and is regulated by various microRNAs. Among them, microRNA-335-3p and microRNA-145-5p, regulated by DNA methylation, have tumor suppressor activities. We studied the role of miR-335 and-145 on PD-L1 suppression in breast cancer. The expression of miR-355 and miR-145 was significantly downregulated in BC tissues and cell lines compared to their controls, and their downregulation was negatively correlated with PD-L1 overexpression. In-silico and luciferase reporter systems confirmed that miR-335 and-145 target PD-L1. In BC tissues and cell lines, cancer-specific methylation was found in CpGrich areas upstream of miR-335 and-145, and up-regulation of PD-L1 expression was connected with hypermethylation (r = 0.4089, P = 0.0147, and r = 0.3373, P = 0.0475, respectively). The higher levels of miR-355 and-145 in BC cells induced apoptosis, arrested the cell cycle, and reduced proliferation significantly. In summary, we found that miR-335 and-145 are novel tumor suppressors inactivated in BC, and these miRs may serve as potential therapeutic targets for breast cancer treatment. Abbreviations PD-L1 Programmed cell death ligand 1 BC Breast cancer miR-335 MicroRNA-335-3p miR-145 MicroRNA-145-5p HRM High Resolute Melting PI Propidium iodide FDA Food and Drug Administration Breast cancer (BC) is the most common cancer among women worldwide, as in 2021 1 , according to the American Cancer Society, an estimated 281,550 women are expected to be diagnosed with breast cancer, and 43,600 women in the US are predicted to die due to breast cancer. While an increasing number of patients can be treated with surgery, radiation, and systemic therapies, a sizable minority are resistant to systemic therapy 2,3. In recent years, the treatment of BC has made significant progress, leading to the development of targeted treatment 2-4. One of the most likely candidates for tumor immune-microenvironment in the incidence of BC is the change of PD-L1 expression 5. The interaction of programmed cell death 1 (PD-1) receptor-ligand (PD-L1 or PD-L2) by tumors was highlighted as a significant inhibitory pathway to suppress immune control and inhibit T-cell activity 6-9. PD-L1 overexpression in BC disrupts the immune system, making it one of the most promising immunotherapy targets for BC 10. Additionally, PD-L1 molecules on tumor cells can predict treatment response and survival prognosis. Breast cancer is highly heterogeneous at the molecular and clinical level 11. The molecular characterization of BC cells demonstrates epigenetic changes, such as miRs' aberrant expression, that silence many genes. MiRNA dysregulation may contribute to the pathogenesis of BC 12-14. miRs can function as tumor suppressors or
Background: The MYC gene is one of the regulatory and proto-oncogenic genes overexpressed in most... more Background: The MYC gene is one of the regulatory and proto-oncogenic genes overexpressed in most prostate cancers (PCa). Studies have shown that abnormal expression of microRNAs is involved in the onset and development of many different types of human cancer, including prostate cancer. Methods and result: In this study, we first evaluated targeting the effect of miR-377 on MYC by luciferase assay. Real-time PCR was used to determine whether miR-377 could decrease the MYC mRNA in transfected PCa cell lines (PC-3 and DU145). Also, the expression of BCL-2/Bax, PTEN, and CDK4 mRNA levels were measured due to MYC degression. Also, the effects of miR-377 on apoptosis cells, proliferation, cell cycle, and wound healing were analyzed. We showed that miR-377 targets MYC mRNA by luciferase reporter assay. A significant reduction in MYC mRNA level was detected following miR-377 transfection in PC-3 and DU145 cell lines. Also, we demonstrated the decrease of BCL-2 and CDK4 and an increase in B...
Aims The MYC gene is one of the regulatory and proto-oncogenic genes that is overexpressed in mos... more Aims The MYC gene is one of the regulatory and proto-oncogenic genes that is overexpressed in most prostate cancers. Studies have shown that abnormal expression of microRNAs is involved in the onset and development of many different types of human cancer, including prostate cancer. Materials and methods In this study, we first evaluated targeting the effect of miR-377 on MYC by luciferase assay. Real-time PCR was used to figure out whether miR-377 could decrease the target gene mRNAs in transfected PCa cell lines (PC3 and DU145). The effects of miR-377 on apoptosis cells, proliferation, cell cycle, and wound healing were analyzed. Results We showed that miR-377 targets MYC mRNA by luciferase reporter assay. A significant reduction in MYC mRNA level was detected, following miR-377 transfection in PC3 and DU145 cell lines. The higher levels of miR-377 in PCa cell lines induced apoptosis, reduced proliferation, and migration, and stopped the cell cycle. Conclusion All these data reveal...
Non-coding RNAs, including Inc-RNA and miRNA, had been reported to regulate gene expression and w... more Non-coding RNAs, including Inc-RNA and miRNA, had been reported to regulate gene expression and were associated with cancer progression. MicroRNA-561-3p (miR-561-3p), as a tumor suppressor, has been reported to play a role in preventing cancer cell progression, and MALAT1 (Lnc-RNA) has also been demonstrated to promote malignancy in various cancer, such as breast cancer (BC). In this study, we aimed to determine the correlation between miR-561-3p and MALAT1 and their roles in breast cancer progression. The expression of MALAT1, mir-561- 3p, and topoisomerase alpha 2 (TOP2A) as a target of miR-561-3p was determined in BC clinical samples and cell lines via qRT-PCR. The binding site between MALAT1, miR-561-3p, and TOP2A was investigated by performing the dual luciferase reporter assay. MALAT1 was knocked down by siRNA, and cell proliferation, apoptotic assays, and cell cycle arrest were evaluated. MALAT1 and TOP2A were significantly upregulated, while mir-561-3p expression was downreg...
PD-L1 is one of the most important immune checkpoint molecules in breast cancer that plays an imp... more PD-L1 is one of the most important immune checkpoint molecules in breast cancer that plays an important role in suppressing the immune system when confronted with tumor cells and is regulated by various microRNAs. Among them, microRNA-335-3p and microRNA-145-5p, regulated by DNA methylation, have tumor suppressor activities. We studied the role of miR-335 and − 145 on PD-L1 suppression in breast cancer. The expression of miR-355 and miR-145 was significantly downregulated in BC tissues and cell lines compared to their controls, and their downregulation was negatively correlated with PD-L1 overexpression. In-silico and luciferase reporter systems confirmed that miR-335 and-145 target PD-L1. In BC tissues and cell lines, cancer-specific methylation was found in CpG-rich areas upstream of miR-335 and-145, and up-regulation of PD-L1 expression was connected with hypermethylation (r = 0.4089, p = 0.0147, and r = 0.3373, p = 0.0475, respectively). The higher levels of miR-355 and − 145 in...
Iranian Journal of Breast Diseases
Nephrology Dialysis Transplantation, 2015
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Papers by sara hajibabaei