Increased Exosomal MicroRNA-21 and MicroRNA-146a Levels in the Cervicovaginal Lavage Specimens of Patients with Cervical Cancer

Well-run screening programs for cervical cancer in the population at risk have been shown to result in a sharp decrease in the incidence and mortality of cervical cancer in a number of large populations. Expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type and developmental origin. Several tumors have been reported to actively release exosomes carrying microRNAs. The present study has determined the association of microRNAs with cervical cancer-derived exosomes. The cervical cancer-derived exosomes were enriched in the cervicovaginal lavages specimens and the abundance of exosomes and exosomal microRNAs was detected by electron microscopy, western blot analysis, RT-qPCR and microRNA target reporter vector. The microRNA-21 and microRNA-146a, which were up-regulated in cervical cancer patients, were associated with the high levels of cervical cancer-derived exosomes. In conclusion, we demonstrated the abundance of exosomes in the cervicovaginal lavage specimens of women with cervical cancer. Furthermore, our results indicated that abnormally high levels of microRNA-21 and microRNA-146a existed in the cervical cancer-derived exosomes and the two microRNAs were functional in 293T cells.     

Fetuin-A Promotes 3-Dimensional Growth in LNCaP Prostate Cancer Cells by Sequestering Extracellular Vesicles to Their Surfaces to Act as Signaling Platforms

The present studies were conducted to evaluate key serum proteins and other components that mediate anchorage-independent growth (3-D growth) of LNCaP prostate cancer cells as spheroids. The cells were cultured on ultra-low attachment plates in the absence and presence of fetuin-A and with or without extracellular vesicles. The data show that fetuin-A (alpha 2HS glycoprotein) is the serum protein that mediates 3-D growth in these cells. It does so by sequestering extracellular vesicles of various sizes on the surfaces of rounded cells that grow as spheroids. These vesicles in turn transmit growth signals such as the activation of AKT and MAP kinases in a pattern that differs from the activation of these key growth signaling pathways in adherent and spread cells growing in 2-D. In the process of orchestrating the movement and disposition of extracellular vesicles on these cells, fetuin-A is readily internalized in adhered and spread cells but remains on the surfaces of non-adherent cells. Taken together, our studies suggest the presence of distinct signaling domains or scaffolding platforms on the surfaces of prostate tumor cells growing in 3-D compared to 2-D.     

Effects of miRNA-149-5p and Platelet-Activating Factor-Receptor Signaling on the Growth and Targeted Therapy Response on Lung Cancer Cells

Accumulating evidence indicates that microRNAs (miRs) play critical roles in essentially all biological processes and their altered expression has been documented in various disease conditions, including human malignancies. Although several cellular mechanisms have been identified in mediating the effects of miRs, the involvement of G-protein-coupled, platelet-activating factor-receptor (PAFR) signaling in miR-149-5p-induced effects on lung cancer growth and therapeutic potential has not been studied. To that end, we first evaluated the functional significance of PAFR and miR-149-5p in A549 and H1299 human non-small cell lung cancer (NSCLC) cell lines. We observed that these tumor lines express endogenous PAFR and miR-149-5p and that PAFR activation by PAF agonist (CPAF) significantly increased, whereas miR-149-5p mimic transfection inhibited cell proliferation in a dose-dependent manner. Interestingly, miR-149-5p mimic significantly attenuated CPAF-mediated increased proliferation of NSCLC cells, as confirmed by miR-149-5p, cyclin D1, and forkhead box protein M1 (FOXM1) expression analysis via qPCR. Our next studies examined PAFR- and miR-149-5p-mediated effects on targeted therapy (i.e., erlotinib and gefitinib) responses. We observed that erlotinib and gefitinib inhibited A549 and H1299 cell survival in a dose- and time-dependent manner, and CPAF significantly blocked this effect. These findings indicate that miR-149-5p blocks PAFR-mediated increased cell proliferation, and PAFR activation attenuates the cytotoxic effects of targeted therapy.     

A Single Variant in Pri-miRNA-155 Associated with Susceptibility to Hereditary Breast Cancer Promotes Aggressiveness in Breast Cancer Cells

Variants in genes encoding for microRNAs have been associated with their deregulation in breast cancer (BC). Sequencing of microRNAs deregulated in BC was performed using DNA from Chilean patients with a strong family history and negative for mutations in BRCA1/BRCA2. Seventeen variants were identified, three of which were selected for a case-control association study: rs376491654 (miR-335), rs755634302 (miR-497), and rs190708267 (miR-155). For rs190708267 C>T, the heterozygous T allele was detected in four BC cases and absent in controls, while homozygous TT cases were not detected. Variants were modelled in silico, cloned in a plasmid, expressed in BC cell lines, and functional in vitro assays were performed. Overexpression of the miR-155-T allele increased mature miR-155-5p levels in both BC cell lines, suggesting that its presence alters pre-miR-155 processing. Moreover, BC cells overexpressing the miR-155-T allele showed increased proliferation, migration, and resistance to cisplatin-induced death compared to miR-155-C overexpressing cells. Of note, the 3′UTR of APC, GSK3β, and PPP1CA genes, all into the canonical Wnt signaling pathway, were identified as direct targets. APC and GSK3β mRNA levels decreased while PP1 levels increased. These results suggest a pathogenic role of the variant rs190708267 (miR-155) in BRCA 1/2 negative BC, conferring susceptibility and promoting traits of aggressiveness.     

Targeting the S100A2-p53 Interaction with a Series of 3,5-Bis(trifluoromethyl)benzene Sulfonamides: Synthesis and Cytotoxicity

In silico approaches identified 1 , N-(6-((4-bromo- benzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzene sulfonamide, as a potential inhibitor of the S100A2-p53 protein-protein interaction, a validated pancreatic cancer drug target. Subsequent cytotoxicity screening revealed it to be a 2.97 μM cell growth inhibitor of the MiaPaCa-2 pancreatic cell line. This is in keeping with our hypothesis that inhibiting this interaction would have an anti-pancreatic cancer effect with S100A2, the validated PC drug target. A combination of focused library synthesis (three libraries, 24 compounds total) and cytotoxicity screening identified a propyl alkyl diamine spacer as optimal; the nature of the terminal phenyl substituent had limited impact on observed cytotoxicity, whereas N-methylation was detrimental to activity. In total 15 human cancer cell lines were examined, with most analogues showing broad-spectrum activity. Near uniform activity was observed against a panel of six pancreatic cancer cell lines: MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, HPAC and PANC-1. In all cases there was good to excellent correlation between the predicted docking pose in the S100A2-p53 binding groove and the observed cytotoxicity, especially in the pancreatic cancer cell line with high endogenous S100A2 expression. This supports S100A2 as a pancreatic cancer drug target.     

Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines

Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked to carcinogenesis. E6 induces anti-apoptosis by degrading tumor suppressor proteins p53 (p53) via E6-E6-associated protein (E6AP)-mediated polyubiquitination. Thus, the restoration of apoptosis by interfering with the E6 function has been proposed as a selective medicinal strategy. This study aimed to determine the activities of andrographolide (Androg) on the disturbance of E6-mediated p53 degradation in cervical cancer cell lines using a proteomic approach. These results demonstrated that Androg could restore the intracellular p53 level, leading to apoptosis-induced cell death in HPV16-positive cervical cancer cell lines, SiHa and CaSki. Mechanistically, the anti-tumor activity of Androg essentially relied on the reduction in host cell proteins, which are associated with ubiquitin-mediated proteolysis pathways, particularly HERC4 and SMURF2. They are gradually suppressed in Androg-treated HPV16-positive cervical cancer cells. Collectively, the restoration of p53 in HPV16-positive cervical cancer cells might be achieved by disruption of E3 ubiquitin ligase activity by Androg, which could be an alternative treatment for HPV-associated epithelial lesions.     

MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2

Aberrant expression of microRNAs (miRNAs) is involved in the development and progression of various types of cancers. In this study, we investigated the role of miR-331-3p in cell proliferation and the expression of keratinocyte differentiation markers of uterine cervical cancer cells. Moreover, we evaluated whether neuropilin 2 (NRP2) are putative target molecules that regulate the human papillomavirus (HPV) related oncoproteins E6 and E7. Cell proliferation in the human cervical cancer cell lines SKG-II, HCS-2, and HeLa was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cellular apoptosis was measured using the TdT-mediated dUTP nick end labeling (TUNEL) and Annexin V assays. Quantitative RT-PCR was used to measure the messenger RNA (mRNA) expression of the NRP2, E6, E7, p63, and involucrin (IVL) genes. A functional assay for cell growth was performed using cell cycle analyses. Overexpression of miR-331-3p inhibited cell proliferation, and induced G2/M phase arrest and apoptosis in SKG-II, HCS-2 and HeLa cells. The luciferase reporter assay of the NRP2 3′-untranslated region revealed the direct regulation of NRP2 by miR-331-3p. Gene expression analyses using quantitative RT-PCR in SKG-II, HCS-2, and HeLa cells overexpressing miR-331-3p or suppressing NRP2 revealed down-regulation of E6, E7, and p63 mRNA and up-regulation of IVL mRNA. Moreover, miR-331-3p overexpression was suppressed NRP2 expression in protein level. We showed that miR-331-3p and NRP2 were key effectors of cell proliferation by regulating the cell cycle, apoptosis. NRP-2 also regulates the expression of E6/E7 and keratinocyte differentiation markers. Our findings suggest that miR-331-3p has an important role in regulating cervical cancer cell proliferation, and that miR-331-3p may contribute to keratinocyte differentiation through NRP2 suppression. miR-331-3p and NRP2 may contribute to anti-cancer effects.     

Tumor Suppressive Role of miR-342-5p in Human Chondrosarcoma Cells and 3D Organoids

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.     

Multistep Model of Cervical Cancer: Participation of miRNAs and Coding Genes

Aberrant miRNA expression is well recognized as an important step in the development of cancer. Close to 70 microRNAs (miRNAs) have been implicated in cervical cancer up to now, nevertheless it is unknown if aberrant miRNA expression causes the onset of cervical cancer. One of the best ways to address this issue is through a multistep model of carcinogenesis. In the progression of cervical cancer there are three well-established steps to reach cancer that we used in the model proposed here. The first step of the model comprises the gene changes that occur in normal cells to be transformed into immortal cells (CIN 1), the second comprises immortal cell changes to tumorigenic cells (CIN 2), the third step includes cell changes to increase tumorigenic capacity (CIN 3), and the final step covers tumorigenic changes to carcinogenic cells. Altered miRNAs and their target genes are located in each one of the four steps of the multistep model of carcinogenesis. miRNA expression has shown discrepancies in different works; therefore, in this model we include miRNAs recording similar results in at least two studies. The present model is a useful insight into studying potential prognostic, diagnostic, and therapeutic miRNAs.     

Synthesis and Evaluation of a Class of Compounds Inhibiting the Growth of Stromal Antigen 2 (STAG2)-Mutant Ewing Sarcoma Cells

STAG2 (SA2) is a critical component of the cohesin complex that regulates gene expression and the separation of sister chromatids in cells. Mutations in STAG2 have been identified in over thirty different types of cancers including myeloid leukaemia, non-small cell lung, bladder and Ewing sarcoma. Selectively inhibiting cancer cells lacking of STAG2 is an attractive approach for the cancer therapy. Here we report that a small molecule, StagX1, identified through a high-throughput screening, inhibits the growth of Ewing sarcoma cells possessing mutant STAG2. A new synthetic route to the StagX1 scaffold and new versions of the molecule along with their activity in a cell viability assay are reported.     

经肛管内外括约肌间隙径路保肛手术临床研究

目的探讨经肛管内外括约肌间径路切除超低位直肠癌保肛手术的安全可行性,并评价肿瘤根治效果及术后肛门功能。方法分析2000年至2008年我院经选择的经肛门内外括约肌间径路切除超低位直肠癌保肛手术病46例的临床资料。结果腹部手术遵循TME原则,肛门手术在直视下距病灶下缘2cm切断直肠黏膜和肛门内括约肌,经括约肌间隙向上游离达肛管外括约肌环上方与腹部手术会合,近端结肠与肛管完成端端吻合。前瞻性随访术后病人肿瘤复发与肛门排便功能状况。38例病人完成手术,并发症包括发生急性肺栓塞并死亡1例,盆底肌肉出血1例,吻合口漏4例。37例病人获得随访,平均随访时间为48(24～96)个月。4例(10.8%)吻合口复发,其中2例死亡;2例同时肺、腹膜转移于术后20个月死亡;2例因肝转移分别于术后18、26个月死亡;2例因腹腔内淋巴结、腹股沟淋巴结转移分别于术后14、17个月死亡。术后6个月肛门括约肌功能已比较满意。结论经肛门内外括约肌间径路切除术治疗超低位直肠癌的手术方法是一种可选择的安全性高、根治效果好的保肛术式。     

Pan-Cancer Prediction of Cell-Line Drug Sensitivity Using Network-Based Methods

The development of reliable predictive models for individual cancer cell lines to identify an optimal cancer drug is a crucial step to accelerate personalized medicine, but vast differences in cancer cell lines and drug characteristics make it quite challenging to develop predictive models that result in high predictive power and explain the similarity of cell lines or drugs. Our study proposes a novel network-based methodology that breaks the problem into smaller, more interpretable problems to improve the predictive power of anti-cancer drug responses in cell lines. For the drug-sensitivity study, we used the GDSC database for 915 cell lines and 200 drugs. The theory of optimal mass transport was first used to separately cluster cell lines and drugs, using gene-expression profiles and extensive cheminformatic drug features, represented in a form of data networks. To predict cell-line specific drug responses, random forest regression modeling was separately performed for each cell-line drug cluster pair. Post-modeling biological analysis was further performed to identify potential biological correlates associated with drug responses. The network-based clustering method resulted in 30 distinct cell-line drug cluster pairs. Predictive modeling on each cell-line-drug cluster outperformed alternative computational methods in predicting drug responses. We found that among the four drugs top-ranked with respect to prediction performance, three targeted the PI3K/mTOR signaling pathway. Predictive modeling on clustered subsets of cell lines and drugs improved the prediction accuracy of cell-line specific drug responses. Post-modeling analysis identified plausible biological processes associated with drug responses.     

Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.     

The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer—An Update

Globally in 2020, an estimated ~600,000 women were diagnosed with and 340,000 women died from cervical cancer. Compared to 2012, the number of cases increased by 7.5% and the number of deaths increased by 17%. MiRNAs are involved in multiple processes in the pathogenesis of cervical cancer. Dysregulation of miRNAs in the pre-stage of cervical cancer is the focus of this review. Here we summarize the dysregulated miRNAs in clinical samples from cervical pre-cancer patients and relate them to the early transformation process owing to human papillomavirus (HPV) infection in the cervical cells. When HPV infects the normal cervical cells, the DNA damage response is initiated with the involvement of HPV’s E1 and E2 proteins. Later, cell proliferation and cell death are affected by the E6 and E7 proteins. We find that the expressions of miRNAs in cervical pre-cancerous tissue revealed by different studies seldom agreed with each other. The discrepancy in sample types, samples’ HPV status, expression measurement, and methods for analysis contributed to the non-aligned results across studies. However, several miRNAs (miR-34a, miR-9, miR-21, miR-145, and miR-375) were found to be dysregulated across multiple studies. In addition, there are hints that the DNA damage response and cell growth response induced by HPV during the early transformation of the cervical cells are related to these miRNAs. Currently, no review articles analyse the relationship between the dysregulated miRNAs in cervical pre-cancerous tissue and their possible roles in the early processes involving HPV’s protein encoded by the early genes and DNA damage response during normal cell transformation. Our review provides insight on spotting miRNAs involved in the early pathogenic processes and pointing out their potential as biomarker targets of cervical pre-cancer.     

Heterogeneous Off-Target Effects of Ultra-Low Dose Dimethyl Sulfoxide (DMSO) on Targetable Signaling Events in Lung Cancer In Vitro Models

Targetable alterations in cancer offer novel opportunities to the drug discovery process. However, pre-clinical testing often requires solubilization of these drugs in cosolvents like dimethyl sulfoxide (DMSO). Using a panel of cell lines commonly used for in vitro drug screening and pre-clinical testing, we explored the DMSO off-target effects on functional signaling networks, drug targets, and downstream substrates. Eight Non-Small Cell Lung Cancer (NSCLC) cell lines were incubated with three concentrations of DMSO (0.0008%, 0.002%, and 0.004% v/v) over time. Expression and activation levels of 187 proteins, of which 137 were kinases and downstream substrates, were captured using the Reverse Phase Protein Array (RPPA). The DMSO effect was heterogeneous across cell lines and varied based on concentration, exposure time, and cell line. Of the 187 proteins measured, all were statistically different in at least one comparison at the highest DMSO concentration, followed by 99.5% and 98.9% at lower concentrations. Only 46% of the proteins were found to be statistically different in more than 5 cell lines, indicating heterogeneous response across models. These cell line specific alterations modulate response to in vitro drug screening. Ultra-low DMSO concentrations have broad and heterogeneous effects on targetable signaling proteins. Off-target effects need to be carefully evaluated in pre-clinical drug screening and testing.     

MicroRNA 3928 Suppresses Glioblastoma through Downregulation of Several Oncogenes and Upregulation of p53

Glioblastoma (GBM) is the most frequent and lethal primary malignant brain tumor. Despite decades of research, therapeutic advances that significantly prolong life are non-existent. In recent years, microRNAs (miRNAs) have been a focus of study in the pathobiology of cancer because of their ability to simultaneously regulate multiple genes. The aim of this study was to determine the functional and mechanistic effects of miR-3928 in GBM both in vitro and in vivo. To the best of our knowledge, this is the first article investigating the role of miR-3928 in GBM. We measured endogenous miR-3928 expression levels in a panel of patient-derived GBM tissue samples and cell lines. We found that GBM tissue samples and cell lines express lower levels of miR-3928 than normal brain cortex and astrocytes, respectively. Therefore, we hypothesized that miR-3928 is a tumor suppressive microRNA. We verified this hypothesis by showing that exogenous expression of miR-3928 has a strong inhibitory effect on both cell growth and invasiveness of GBM cells. Stable ex vivo overexpression of miR-3928 in GBM cells led to a reduction in tumor size in nude mice xenografts. We identified many targets (MDM2, CD44, DDX3X, HMGA2, CCND1, BRAF, ATOH8, and BMI1) of miR-3928. Interestingly, inhibition of the oncogene MDM2 also led to an upregulation of wild-type p53 expression and phosphorylation. In conclusion, we find that miR-3928, through the downregulation of several oncogenes and upregulation and activation of wild-type p53, is a strong tumor suppressor in GBM. Furthermore, the fact that miR-3928 can target many important dysregulated proteins in GBM suggests it might be a “master” regulatory microRNA that could be therapeutically exploited.     

Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.     

Involvement of miR-20a in Promoting Gastric Cancer Progression by Targeting Early Growth Response 2 (EGR2)

Gastric cancer (GC) is one of the most common cancers, with high incidences in East Asia. microRNAs (miRNAs) play essential roles in the carcinogenesis of GC. miR-20a was elevated in GC, while the potential function of miR-20a was poorly understood. miR-20a expression was examined in GC tissues and cell lines. The effects of miR-20a on the growth, migration, invasion, and chemoresistance of GC cells were examined. Luciferase reporter assay and Western blot were used to screen the target of miR-20a. miR-20a was increased in GC tissues and cell lines. miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a. miR-20a was involved in the carcinogenesis of GC through modulation of the EGR2 signaling pathway.