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

Abstract

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.

Silencing of HMGA2 by siRNA Loaded Methotrexate Functionalized Polyamidoamine Dendrimer for Human Breast Cancer Cell Therapy

“…Looking at the results of cell viability assay, we find that G4/MTX containing HMGA2 siRNA is a more effective treatment to reduce cell viability than other treatment groups, which maybe a result of the synergistic effect of two therapeutic agents (MTX and HMGA2 specific siRNA) on cancer cells via efficiently exerting cell death in complementary pathways. In agreement with our study, Naghizadeh et al concluded that, following the use of siRNA against HMGA2, cell proliferation is significantly inhibited [ 42 ]. Apoptosis is a fundamental process that occurs in multicellular organisms in order to eliminate abnormal or unsensational cells and is responsible for different biological functions [ 43 ].…”

Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression

“…In addition, HMGA2 level is an independent biomarker of NSCLC prognosis [29]. Functionally, HMGA2 has been confirmed as an oncogene during NSCLC initiation and progression [30][31][32]. Here, we proved that HMGA2 expression is positively regulated by VPS9D1-AS1 in NSCLC; further, we showed that this regulatory effect is essential for the tumorigenic actions of VPS9D1-AS1 in NSCLC cells.…”

“…The bioinformatics prediction indicated that a site in the 3′-UTR of HMGA2 mRNA matched the "seed sequence" of miR-532-3p ( Figure 4F). HMGA2 was selected for further verification because that this gene was reported to be overexpressed in NSCLC and exert crucial roles during NSCLC initation and progression [29][30][31][32]. A luciferase reporter assay was then performed to demonstrate the possibility of miR-532-3p binding to the 3′-UTR of HMGA2 mRNA in NSCLC cells.…”

Hydrophobically Modified let-7b miRNA Enhances Biodistribution to NSCLC and Downregulates HMGA2 In Vivo

“…Our research in the present study addresses the potential of a novel therapeutic approach combining a lipid and hydrophobically modified let-7b miRNA that can be useful to target NSCLC with silencing of HMGA2 mRNA. Indeed, the presence of high levels of HMGA2 mRNA has been observed with lung cancer 2 , 5 , 6 , 58 , 59…”

“…let-7 encodes a microRNA (miRNA) that targets HMGA2 in lung cancer 1, 2, 3, 4, 5, 6. Lung cancer is responsible for the most cancer-related deaths for both men and women in the US with an estimated 224,390 new cases and 158,080 deaths from the disease in 2016 7 .…”