COVID-19 Infection: Concise Review Based on the Immunological Perspective.

The outbreak of coronavirus disease 2019 (COVID-19) has posed a serious threat to public health. There is an urgent need for discovery methods for the prevention and treatment of COVID-19 infection. Understanding immunogenicity together with immune responses are expected to provide further information about this virus. We hope that this narrative review article may create new insights for researchers to take great strides toward designing vaccines and novel therapies in the near future. The functional properties of the immune system in COVID-19 infection is not exactly clarified yet. This is compounded by the many gaps in our understanding of the SARS-CoV-2 immunogenicity properties. Possible immune responses according to current literature are discussed as the first line of defense and acquired immunity. Here, we focus on proposed modern preventive immunotherapy methods in COVID-19 infection.

Targeted Therapy of B7 Family Checkpoints as an Innovative Approach to Overcome Cancer Therapy Resistance: A Review from Chemotherapy to Immunotherapy.

It is estimated that there were 18.1 million cancer cases worldwide in 2018, with about 9 million deaths. Proper diagnosis of cancer is essential for its effective treatment because each type of cancer requires a specific treatment procedure. Cancer therapy includes one or more approaches such as surgery, radiotherapy, chemotherapy, and immunotherapy. In recent years, immunotherapy has received much attention and immune checkpoint molecules have been used to treat several cancers. These molecules are involved in regulating the activity of T lymphocytes. Accumulated evidence shows that targeting immune checkpoint regulators like PD-1/PD-L1 and CTLA-4 are significantly useful in treating cancers. According to studies, these molecules also have pivotal roles in the chemoresistance of cancer cells. Considering these findings, the combination of immunotherapy and chemotherapy can help to treat cancer with a more efficient approach. Among immune checkpoint molecules, the B7 family checkpoints have been studied in various cancer types such as breast cancer, myeloma, and lymphoma. In these cancers, they cause the cells to become resistant to the chemotherapeutic agents. Discovering the exact signaling pathways and selective targeting of these checkpoint molecules may provide a promising avenue to overcome cancer development and therapy resistance. Highlights: (1) The development of resistance to cancer chemotherapy or immunotherapy is the main obstacle to improving the outcome of these anti-cancer therapies. (2) Recent investigations have described the involvement of immune checkpoint molecules in the development of cancer therapy resistance. (3) In the present study, the molecular participation of the B7 immune checkpoint family in anticancer therapies has been highlighted. (4) Targeting these immune checkpoint molecules may be considered an efficient approach to overcoming this obstacle.

Resistance mechanisms to immune checkpoints blockade by monoclonal antibody drugs in cancer immunotherapy: Focus on myeloma.

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of neoplastic proliferation of a plasma cell in the bone marrow that produces a monoclonal immunoglobulin. The immune checkpoint inhibitors against programmed death-1/programmed death-1 ligand and cytotoxic T-lymphocyte antigen 4 axis have demonstrated appropriate anticancer activity in several solid tumors and liquid cancers, and are rapidly transforming the practice of medical oncology. However, in a high percentage of patients, the efficacy of immune checkpoints blockade remains limited due to innate or primary resistance. Moreover, the malignancies progress in many patients due to acquired or secondary resistance, even after the clinical response to immune checkpoints' blockade. The evidence shows that multiple tumor-intrinsic and tumor-extrinsic factors and alterations in signaling pathways are involved in primary and secondary resistance to immune checkpoints blockade. Improved identification of intrinsic and extrinsic factors and mechanisms of resistance or response to immune checkpoints blockade may not only provide novel prognostic or predictive biomarkers but also guide the optimal combination/sequencing of immune checkpoint blockade therapy in the clinic. Here, we review the underlying biology and role of immune checkpoints blockade in patients with MM. Furthermore, we review the host and tumor-related factor effects on immune checkpoints blockade in MM immunotherapy.

Varied functions of immune checkpoints during cancer metastasis.

Immune checkpoints comprise diverse receptors and ligands including costimulatory and inhibitory molecules, which play monumental roles in regulating the immune system. Immune checkpoints retain key potentials in maintaining the immune system homeostasis and hindering the malignancy development and autoimmunity. The expression of inhibitory immune checkpoints delineates an increase in a plethora of metastatic tumors and the inhibition of these immune checkpoints can be followed by promising results. On the other hand, the stimulation of costimulatory immune checkpoints can restrain the metastasis originating from diverse tumors. From the review above, key findings emerged regarding potential functions of inhibitory and costimulatory immune checkpoints targeting the metastatic cascade and point towards novel potential Achilles' heels of cancer that might be exploited therapeutically in the future.

Cholinergic anti-inflammatory pathway and connective tissue diseases.

Connective tissue diseases (CTDs) consist of an extensive range of heterogeneous medical conditions, which are caused by immune-mediated chronic inflammation and influences the various connective tissues of the body. They include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, Sjögren's syndrome, Behcet's disease, and many other autoimmune CTDs. To date, several anti-inflammatory approaches have been developed to reduce the severity of inflammation or its subsequent organ manifestations. As a logical mechanism to harnesses the undesired inflammation, some studies investigated the role of the intrinsic cholinergic anti-inflammatory pathway (CAP) in the modulation of chronic inflammation. Many different experimental and clinical models have been developed to evaluate the therapeutic significance of the CAP in CTDs. On the other hand, an issue that is less emphasized in this regard is the presence of autonomic neuropathy in CTDs, which influences the efficiency of CAP in such clinical settings. This condition occurs during CTDs and is a well-known complication of patients suffering from them. The advantages and limitations of CAP in the control of inflammatory responses and its possible therapeutic benefits in the treatment of CTDs are the main subjects of the current study. Therefore, this narrative review article is provided based on the recent findings of the complicated role of CAP in CTDs which were retrieved by searching Science Direct, PubMed, Google Scholar, and Web of Science. It seems that delineating the complex influences of CAP would be of great interest in designing novel surgical or pharmacological therapeutic strategies for CTDs therapy.

The role of HSP90 molecular chaperones in hepatocellular carcinoma.

Misfolded proteins have enhanced formation of toxic oligomers and nonfunctional protein copies lead to recruiting wild-type protein types. Heat shock protein 90 (HSP90) is a molecular chaperone generated by cells that are involved in many cellular functions through regulation of folding and/or localization of large multi-protein complexes as well as client proteins. HSP90 can regulate a number of different cellular processes including cell proliferation, motility, angiogenesis, signal transduction, and adaptation to stress. HSP90 makes the mutated oncoproteins able to avoid misfolding and degradation and permits the malignant transformation. As a result, HSP90 is an important factor in several signaling pathways associated with tumorigenicity, therapy resistance, and inhibiting apoptosis. Clinically, the upregulation of HSP90 expression in hepatocellular carcinoma (HCC) is linked with advanced stages and inappropriate survival in cases suffering from this kind of cancer. The present review comprehensively assesses HSP90 functions and its possible usefulness as a potential diagnostic biomarker and therapeutic option for HCC.

PD-1/PD-L1-dependent immune response in colorectal cancer.

Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death-1 (PD-1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD-1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD-ligand 1 (PD-L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD-L1 by conventional chemotherapeutics, we have summarized the role of PD-L1 in CRC, the chemotherapy effects on the PD-1/PD-L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD-L1.

Regulatory mechanisms of microRNAs in colorectal cancer and colorectal cancer stem cells.

Colorectal cancer (CRC) is one of the most lethal and hard-to-treat cancers in the world, which in its advanced stages, surgery and chemotherapy are the main common treatment approaches. The microRNAs (miRNAs), as novel markers for CRC detection, promote their regulatory effects via the 3'-untranslated binding region (3'-UTR) of target messenger RNA in posttranscriptional regulation of genes and also play a pivotal role in modulating resistance to chemotherapeutic agents. These small noncoding RNAs have also a critical role in CRC stem cells (CRCSCs) regulation, comprising self-renewal, differentiation, and tumorigenesis. Cancer stem cells (CSCs) are distinctive cell types inside a tumor tissue that are believed to derive from normal somatic stem cells. The CSCs have self-renewal abilities, angiogenesis, as well as specific surface markers expression characteristics. Furthermore, they are frequently criticized for tumor maintenance, treatment resistance, tumor development, and distant metastasis. In this review, we discuss the current understandings of CRCSCs and their environment with a focus on the role of miRNAs on the regulation of CSCs and their targeting application in CRC treatment.

Overcoming trastuzumab resistance in HER2-positive breast cancer using combination therapy.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) comprises around 20-30% of all BC subtypes and is correlated with poor prognosis. For many years, trastuzumab, a monoclonal antibody, has been used to inhibit the HER2 activity. Though, the main resistance to trastuzumab has challenged the use of this drug in the management of HER2-positive BC. Therefore, the determination of resistance mechanisms and the incorporation of new agents may lead to the development of a better blockade of the HER family receptor signaling. During the last few years, some therapeutic drugs have been developed for treating patients with trastuzumab-resistant HER2-positive BC that have more effective influences in the management of this condition. In this regard, the present study aimed at reviewing the mechanisms of trastuzumab resistance and the innovative therapies that have been investigated in trastuzumab-resistant HER2-positive BC subjects.

CD133 suppression increases the sensitivity of prostate cancer cells to paclitaxel.

One of the major barriers in cancer therapy is the resistance to conventional therapies and cancer stem cells (CSCs) are among the main causes of this problem. CD133 as a CSC marker displays stem cell-like properties, tumorigenic capacity, and drug resistance in various cancers. However, the molecular mechanism behind CD133 function in prostate cancer (PC) still remains unclear. This research aimed to illustrate the probabilistic mechanism of CD133-siRNA and paclitaxel in the reduction of chemoresistance in PC cells. To measure the cell viability, migratory capacity, CSCs properties, invasive potential, apoptosis and cell cycle progression of the cells, the MTT, wound healing, spheroid assay, colony formation assay, DAPI staining and flow cytometry assays were applied in the LNCaP cell line, respectively. Also, quantitative real-time PCR (qRT-PCR) and western blot method were used for measuring the expression of CD133 and the effects of CD133 silencing on the AKT/mTOR/c-myc axis and pro-metastatic genes expression. We showed that the CD133-siRNA considerably decreased the CD133 expression. Moreover, CD133-siRNA and paclitaxel treatment significantly decreased cell proliferation and also inhibited the ability of cell migration and invasion and reduced pro-metastatic genes expression. Additionally, we found that the simultaneous use of CD133-siRNA and paclitaxel increased the paclitaxel-induced apoptosis. Our results confirmed that CD133 silencing combined with paclitaxel synergistically could suppress cell migration, invasion, and proliferation and enhance the chemosensitivity compared with mono treatment. Therefore, CD133 silencing therapy could be viewed as a promising and efficient strategy in PC targeted therapies.

Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?

Although the ever-increasing number of cancer patients pose substantial challenges worldwide, finding a treatment with the highest response rate and the lowest number of side effects is still undergoing research. Compared to chemotherapy, the relatively low side effects of cancer immunotherapy have provided ample opportunity for immunotherapy to become a promising approach for patients with malignancy. However, the clinical translation of immune-based therapies requires robust anti-tumoral immune responses. Immune checkpoints have substantial roles in the induction of an immunosuppressive tumor microenvironment and tolerance against tumor antigens. Identifying and targeting these inhibitory axes, which can be established between tumor cells and tumor-infiltrating lymphocytes, can facilitate the development of anti-tumoral immune responses. Bispecific T-cell engagers, which can attract lymphocytes to the tumor microenvironment, have also paved the road for immunological-based tumor elimination. The development of CAR-T cells and their gene editing have brought ample opportunity to recognize tumor antigens, independent from immune checkpoints and the major histocompatibility complex (MHC). Indeed, there have been remarkable advances in developing various CAR-T cells to target tumoral cells. Knockout of immune checkpoints via gene editing in CAR-T cells might be designated for a breakthrough for patients with malignancy. In the midst of this fast progress in cancer immunotherapies, there is a need to provide up-to-date information regarding immune checkpoints, bispecific T-cell engagers, and CAR-T cells. Therefore, this review aims to provide recent findings of immune checkpoints, bispecific T-cell engagers, and CAR-T cells in cancer immunotherapy and discuss the pertained clinical trials.

Small interfering RNA-mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the lethal and difficult-to-cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence-specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA-mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti-HCC agents is the subject of the current review. siRNA-based gene therapies could be one of the main feasible approaches for HCC therapy in the future.

The potential role of miR-29 in health and cancer diagnosis, prognosis, and therapy.

miR-29 family is one of the small noncoding RNAs and has a very important role in many physiologic and pathologic functions through regulating the target genes that play roles in various bioprocesses such as proliferation, survival, apoptosis, and angiogenesis. Thus, we aim to survey the potential of the miR-29 family in normal model and development and progression of malignancy in this study. In addition, the potential role of miR-29 family has been studied as the clinical marker for the diagnosis and prognosis of many cancers as the potential targets to treat cancer. Moreover, it was stated in summary that the herbal compounds can regulate miR-29 family in cancers. Therefore, regulating the expression of the miR-29 family in a variety of cancers can be a new strategy to obtain better results from cancerous patients' treatment in the future.

Alpha7 nicotinic acetylcholine receptors in lung inflammation and carcinogenesis: Friends or foes?

The lung tissue expresses the cholinergic system including nicotinic acetylcholine receptors (nAChRs) which included in many physiologic and pathologic processes. Mounting evidence revealed that these receptors have important roles in lung carcinogenesis via modulating either stimulatory or inhibitory signaling pathways. Among different members of nicotinic receptors family, alpha7-subtype of nAChR (α7nAChR) is a critical mediator involved in both inflammatory responses and cancers. Several studies have shown that this receptor is the most powerful regulator of responses that stimulate lung cancer processes such as proliferation, angiogenesis, metastasis, and inhibition of apoptosis. Moreover, aside from its roles in the regulation of cancer pathways, there is growing evidence indicating that α7nAChR has profound impacts on lung inflammation through the cholinergic anti-inflammatory pathway. Regarding such diverse effects as well as the critical roles of nicotine as an activator of α7nAChR on lung cancer pathogenesis, its modulation has emerged as a promising target for drug developments. In this review, we aim to highlight the detrimental as well as the possible beneficial influences of α7nAChR downstream signaling cascades in the control of lung inflammation and cancer-associated properties. Consequently, by considering the significant global burden of lung cancer, delineating the complex influences of α7 receptors would be of great interest in designing novel anticancer and anti-inflammatory strategies for the patients suffering from lung cancer.

Effects of nicotine on microRNA-124 expression in bile duct ligation-induced liver fibrosis in rats.

BACKGROUND: Nicotine, the main compound of smoking may exert its effects by changing the expression of microRNAs (miRNAs). This study was conducted to further investigate the molecular mechanisms of miRNA-dependent effects of nicotine in an animal model of liver fibrosis. METHODS: The bile duct ligation (BDL) approach was used to create a model of liver fibrosis. Twenty-four male Wistar rats were used in the study. The effects of nicotine administration on miRNA-124 expression, as well as alpha-smooth muscle actin (liver fibrosis marker) and chemokine ligand 2 (an inflammatory chemokine), were investigated using RT-qPCR. In addition, the mRNA and protein expression of signal transducer and activator of transcription 3 (STAT-3; as a potential target for miRNA-124) were investigated by RT-qPCR and immunofluorescence, respectively. Liver enzyme activity levels were measured using a colorimetric assay. In addition, the effects of nicotine on the process of liver fibrosis were investigated with histological studies. RESULTS: The development of liver fibrosis in BDL rats and nicotine administration led to a decrease in miRNA-124 expression. The decrease in the expression is accompanied by the increase in the expression of fibrotic and proinflammatory genes. Also, an increase in STAT-3 mRNA and protein expression was observed in the fibrotic rats that received nicotine. In addition, the significant increase in bilirubin and liver enzymes in fibrotic rats worsens with nicotine administration. The results of histological studies also confirm these results. CONCLUSION: Considering that miRNA-124 is an anti-inflammatory miRNA, it can be concluded that the decrease in its expression due to nicotine exposure leads to an increase in inflammatory processes and subsequently to an increase in liver fibrosis.

Nicotine promotes development of bile duct ligation-induced liver fibrosis by increasing expression of nicotinic acetylcholine receptors in rats.

Aim of the study: Liver fibrosis and cigarette smoking seem to be directly linked. Nicotine, as an agonist of nicotinic acetylcholine receptors (nAChRs), induces many downstream signaling pathways. The pathways through which nicotine affects the process of liver fibrosis have not been clarified. The present study aimed to investigate the nicotine-induced effects on fibrosis progression in cholestatic rats. Material and methods: First, the Wistar rats were subjected to sham or bile duct ligation (BDL) surgery. The rats were treated with low and high doses of nicotine (1 or 10 mg/kg) for three weeks. They were monitored for their body weights before and 21 days after BDL. Also, spleens were weighed to calculate the spleen/body weight ratio. Ductular proliferation and fibrosis were evaluated using hematoxylin and eosin (H&E) as well as Masson's trichrome staining. The mRNA expression of α4nAChR, α7nAChR, and fibrosis gene α-smooth muscle actin (α-SMA) was measured by real-time PCR. Results: The findings showed that nicotine promotes the development of BDL-induced liver fibrosis. The ratio of spleen/body weight was significantly affected by nicotine exposure. H&E and Masson's trichrome staining showed that the level of liver fibrosis was higher in the cholestatic BDL groups, and this effect was significantly augmented in the nicotine-treated rats. Also, α4nAChR, α7nAChR, and α-SMA expression was observed in the BDL rats and increased following nicotine treatment. Conclusions: The activation of nAChR triggers biliary proliferation and liver fibrosis. Studying the intracellular mechanism of nicotine and alteration in the expression of nicotinic receptors following nicotine exposure can be useful both in diagnosing nicotine-related diseases and finding new treatment strategies.

The role of microRNAs in nicotine signaling.

Cigarette smoking is a harmful habit that is widespread around the world. It is among the well-known lifestyle-related risk factors for many diseases. Nicotine, as its principal constituent, has various detrimental, and beneficial functions. Nicotinic acetylcholine receptors (nAChRs), which are present in nearly all body cells, are how nicotine works. Numerous investigations have demonstrated that nicotine causes abnormal microRNA expression (miRNAs). These short sequences of RNAs are known to regulate gene expression post-transcriptionally. A wide range of miRNAs are modulated by nicotine, and nicotine-induced miRNA changes could subsequently mediate nicotine's effect on gene expression regulation. We will focus on the reciprocal interaction between nAChRs and miRNAs and describe the essential targets of these dysregulated miRNAs after nicotine exposure and activation of nAChRs. It appears that crucial subcellular mechanisms implicated in nicotine's effects are miRNA-related pathways. It is crucial to investigate the molecular mechanism underlying the effects of nicotine as well as the dysregulation of miRNA following nAChR activation. The finding about epigenetic mechanisms of nicotine-induced effects may shed light on the establishment of new treatment strategies to prevent the harmful effects of nicotine and perhaps may augment the beneficial effects in diverse smoking-related diseases.

CTLA-4: As an Immunosuppressive Immune Checkpoint in Breast Cancer.

Breast cancer (BC) is one of the prevalent diseases and causes of death in women, and its incidence rate is increasing in numerous developed and developing countries. The common approach to BC therapy is surgery, followed by radiation therapy or chemotherapy, which doesn't lead to acceptable outcomes in many patients. Therefore, developing innovative strategies for treating BC is essential for the most effective therapy. The immunotherapy of BC is a promising and attractive strategy that can increase the immune system's capacity to recognize and kill the tumor cells, inhibit the recurrence of the tumors, and develop new metastatic sites. The blockade of immune checkpoints is the most attractive and promising strategy for cancer immunotherapy. The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a cellsurface glycoprotein expressed by stimulated T cells and has pivotal roles in cell cycle modulation, cytokine generation, and regulation of T cell proliferation. Currently, anti- CTLA-4 agents such as monoclonal antibodies (Ipilimumab and tremelimumab) are broadly applied as therapeutic agents in clinical studies of different cancers. The anti- CTLA-4 antibodies, alone or combined with other therapeutic agents, remarkably increased the tumor-suppressive effects of the immune system and improved the prognosis of cancer. The immune checkpoint inhibitors may represent promising options for BC treatment as in monotherapy or in combination with other conventional treatments. In this review, we discuss the role of CTLA-4 and its therapeutic potential by inhibitors of immune checkpoints in BC therapeutics.

The role of microRNAs in hepatocellular carcinoma: Therapeutic targeting of tumor suppressor and oncogenic genes.

Hepatocellular carcinoma (HCC) is a severe malignant liver cancer with a poor prognosis and a high mortality rate. This carcinoma is a multistage process that begins with chronic hepatitis and progresses to cirrhosis, dysplastic nodules, and eventually HCC. However, the exact molecular etiology remains unclear. MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of numerous genes. These molecules have become significant participants in several functions, including cell proliferation, differentiation, development, and tumorrelated properties. They have a pivotal role in carcinogenesis as oncogenes or tumor suppressor genes. Furthermore, some investigations have shown that particular miRs might be used as predictive or diagnostic markers and therapeutic targets in HCC therapy. This review study summarizes the current level of knowledge on the role of miRs in the initiation and progression of HCC.

Downregulation of HMGA2 by Small Interfering RNA Affects the Survival, Migration, and Apoptosis of Prostate Cancer Cell Line.

Purpose: To investigate the downregulation of high mobility group AT-hook 2 (HMGA2)expression by small interfering RNAs (siRNAs) in PC3 prostate cancer cell line. HMGA2belongs to the non-histone chromatin-binding protein family that serves as a crucial regulator ofgene transcription. The overexpression of this gene is positively correlated with various prostatecancer (PC)-related properties. Thus, HMGA2 is an emerging target in PC treatment. This studyaimed to examine the impact of siRNAs targeting HMGA2 on the viability, migration, andapoptosis processes of the PC3 PC cell line. Methods: siRNA transfection was conducted with a liposome-mediated approach. The mRNAand protein expression levels for HMGA2 are evaluated by real-time polymerase chain reaction(qRT-PCR) and western blot analysis. The cytotoxic properties of HMGA2-siRNA were measuredby MTT assay on PC3 cells. The migration of PC3 cells was measured by implementing awound-healing assay. Apoptosis measurement was also quantified by TUNEL assay. Results: Transfection with siRNA significantly decreased both mRNA and protein levels of theHMGA2 gene in a dose-dependent manner after 48 hours. Also, we demonstrated that theknockdown of HMGA2 led to a reduction in cell viability, migration ability, and enhancedapoptosis of PC3 cells in vitro. Conclusion: Our findings recommend that the specific siRNA of HMGA2 may efficiently beable to decrease PC progression. Therefore, it may be a promising adjuvant treatment in PC.