Effects of HMGA2 siRNA and doxorubicin dual delivery by chitosan nanoparticles on cytotoxicity and gene expression of HT-29 colorectal cancer cell line

Siahmansouri, Homayoon; Somi, Mohammad Hossein; Babaloo, Zohreh; Baradaran, Behzad; Jadidi‐Niaragh, Farhad; Atyabi, Fatemeh; Mohammadi, Hamed; Ahmadi, Majid; Yousefi, Mehdi

doi:10.1111/jphp.12593

Cited by 66 publications

(38 citation statements)

References 44 publications

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“…46 LET7a micRNA showed the same effect by reducing HMGA2 translation, but on 95D cells. 30,33,45 An explanation that could be considered for slightly increase in E-cadherin expression thereafter HMGA2 knockdown is that Ecadherin, which is a member of classical cadherins and is found in adherence junctions to help to sustain cell shape and polarity, is negatively regulated by snail and twist during EMT process. Downregulation of HMGA2 by RNAi in SW480 cells decreased the invasive ability of cells.…”

Section: Discussionmentioning

confidence: 99%

“…16 After separation of duplex fragments by helicase and degradation of sense strand by the endonuclease, the antisense strand is loaded onto RNAinduced silencing complex (RISC). 26,[29][30][31] During EMT process epithelial cells acquire mesenchymal properties and show morphological changes, for example, losing ECM interaction and increased invasive behavior. The mRNA will be cleaved by a member of a RISC called Argonaute 2.…”

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confidence: 99%

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Effects of HMGA2 gene downregulation by siRNA on lung carcinoma cell migration in A549 cell lines

Naghizadeh

Mansoori

Mohammadi

et al. 2018

J of Cellular Biochemistry

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Background Although there are multiple treatments for lung cancer, the death rate of this cancer remains high because of metastasis in earlier stages. So a novel treatment for overcoming metastasis is urgently needed. Overexpression of high‐mobility group AT‐hook 2 (HMGA2), a nonhistone chromosomal protein has been observed in metastatic cancers. So, we suggested that HMGA2 upregulation may play a critical role in treating lung cancer. Methods The A549 cells were transfected with specific HMGA2 small interfering RNA (siRNA) using transfection reagent. Relative HMGA2 and matrix metallopeptidase 1 (MMP1), C‐X‐C chemokine receptor type 4 (CXCR4), vimentin, and E‐cadherin messenger RNA expression levels were measured by quantitative real‐time polymerase chain reaction. To diagnose cytotoxic effect of HMGA2 siRNA and other components of transfection process, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was applied. The migration capacity after transfection with HMGA2 siRNA was detected by wound‐healing assay. Results HMGA2 siRNA significantly reduced HMGA2 expression in a dose‐dependent manner 48 hours after transfection. Expression levels of MMP1, vimentin, and CXCR4 were reduced, but E‐cadherin level was not changed meaningfully. HMGA2 knockdown significantly reduced cell survival rate and also led to the inhibition of cell migration. Conclusions Our results indicated that RNA interference by downregulation of HMGA2 gene expression and affecting downstream genes led to the inhibition of cell migration and proliferation. Therefore, HMGA2 siRNA might be an alternative treatment option for metastatic lung cancer.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Effects of HMGA2 gene downregulation by siRNA on lung carcinoma cell migration in A549 cell lines

Naghizadeh

Mansoori

Mohammadi

et al. 2018

J of Cellular Biochemistry

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“…As cancers present with ever-increasing heterogeneity, siRNA-based therapy is increasingly being explored in combination with chemo- [127], [128], immune- [129]–[131], radiation- [132]–[134], and photodynamic therapies [135]–[137]. While gene silencing using siRNA improves the sensitivity of drug resistant cancer to chemotherapeutics [127] siRNA mediated downregulation of immunosuppressive genes enhances the sensitization of cancer cells towards T cell-mediated killing [129].…”

Section: Challenges and Perspectivesmentioning

confidence: 99%

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Babu

Muralidharan

Amreddy

et al. 2016

IEEE Trans.on Nanobioscience

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Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusses various nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome based gene delivery systems. The discussion also includes various methods availed to improve nanoparticle based-siRNA delivery with target specificity and superior efficiency. Further this review describes challenges and perspectives on the development of safe and efficient nanoparticle based-siRNA-delivery systems for cancer therapy.

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“…[11][12][13][14][15] In an effort to analyze the promoter methylation status of BAX gene in the T47D, MCF-7, MDA-MB-231 cell lines, Alipour et al 16 ruled out the contribution of CpG island hypermethylation on the BAX downregulation. The epigenetic mechanisms, which are defined as mitotically stable changes in gene expression without alterations in DNA backbone, have been shown to play essential roles in pathogenesis of several types of cancers such as breast cancer, colorectal, prostate, and hematopoietic malignancies including acute myeloid leukemia, chronic myeloid leukemia, and ALL.…”

Section: Introductionmentioning

confidence: 99%

Apoptotic effect of resveratrol on human T‐ALL cell line CCRF‐CEM is unlikely exerted through alteration of BAX and BCL2 promoter methylation

Heydarabad

Vatanmakanian

Abdolalizadeh

et al. 2018

J of Cellular Biochemistry

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One of the fundamental barriers leading to failure of leukemia therapy is the resistance against conventional chemotherapies, common modality used to cure leukemia. Having the potential to trigger apoptosis in various human leukemia cell lines, resveratrol is regarded as a robust agent in chemotherapy regimens. The current study was aimed to assess whether the apoptotic effect of resveratrol on T-cell acute lymphoblastic leukemia cell line, CCRF-CEM, is exerted through DNA methylation of BAX and BCL2 gene promoters. For this purpose, the CCRF-CEM cells were treated by resveratrol under standard cell culture. To analyze the promoter DNA methylation changes, we used methylation-specific polymerase chain reaction technique following the resveratrol treatment at different dosages and time intervals. Based on our previous study, the resveratrol treatment can trigger apoptosis in CCRF-CEM cell line via upregulation of apoptotic BAX gene and downregulation of antiapoptotic BCL2 gene. Despite these alterations in gene expression, the current study reveals no changes in DNA methylation patterns of subjected genes following the resveratrol treatment. Unchanged status of DNA methylation of BAX and BCL2 genes may suggest that resveratrol causes the gene expression changes through a distinct mechanism which requires further studies to be understood.

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Effects of HMGA2 siRNA and doxorubicin dual delivery by chitosan nanoparticles on cytotoxicity and gene expression of HT-29 colorectal cancer cell line

Abstract: In conclusion, our results revealed that dual delivery of a key gene siRNA and appropriate anticancer drug have great impact on the treatment of colorectal cancer.

Cited by 66 publications

References 44 publications

Effects of HMGA2 gene downregulation by siRNA on lung carcinoma cell migration in A549 cell lines

Effects of HMGA2 gene downregulation by siRNA on lung carcinoma cell migration in A549 cell lines

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Apoptotic effect of resveratrol on human T‐ALL cell line CCRF‐CEM is unlikely exerted through alteration of BAX and BCL2 promoter methylation

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