The effect of antibiotic prophylaxis on the incidence of surgical site infection after laparoscopic appendectomy for chronic appendicitis.

Background: The guidelinesthat specify whether antibiotic prophylaxis should be administered before laparoscopic clean-contaminated wound to prevent postoperative surgical site infection (SSI) need to be improved. Studies have shown that elective laparoscopic cholecystectomy with clean-contaminated wound does not require antibiotic prophylaxis. However, there are no studies on the effect of antibiotic prophylaxis on SSI after laparoscopic appendectomy for chronic appendicitis (LCA), which is a clean-contaminated wound. Methods: We conducted a single-center, double-blind, randomized controlled clinical trial. A total of 106 effective patients were randomly divided into the antibiotic group and saline group. Cefuroxime or clindamycin was administered intravenously in the antibiotic group (n = 52). Saline (0.9%) was administered intravenously in the saline group (n = 54). Interventions were administered as a single dose 30 min before surgery. Results: Among the 106 effective patients (median age, 37 years old [IQR, 25-45]; females, 77 [72.6%]), there were 6 cases (5.70%) of SSI: 3 cases (5.56%) in the saline group and 3 cases (5.70%) in the antibiotic group (OR = 1.00, [95% CI (0.20-5.4)], P = 0.96). There were no significant differences in the clinical outcomes of anal exhaust time, postoperative complications, and the symptom of primary abdominal pain between the two groups. Conclusion: For patients with chronic appendicitis undergoing laparoscopic appendectomy, preoperative intravenous antibiotic prophylaxis did not reduce the risk of SSI within 30 days of the surgery compared to the saline group. Trial registration: Registration number of China Clinical Trials Registration Center: ChiCTR2100048336.

Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial-mesenchymal transition.

Sorafenib, a pan-protein kinase inhibitor, inhibits the activity of various kinases (like vascular endothelial growth factor, platelet-derived growth factor, and rapidly accelerated fibrosarcoma) and clinically has been used to treat different human cancers. This study investigated its antitumor activity in ovarian cancer and the underlying molecular events. To achieve that, ovarian cancer SKOV-3 cells were treated with or without sorafenib (10 µM), transforming growth factor (TGF)-ß1 (10 ng/mL), sorafenib (10 µM) + TGF-ß1 (10 ng/mL), and TGF-ß1 (10 ng/mL) + Ly2157299 (5 µM), followed by 8-Gy radiation. The cells were then subjected to cell viability, wound healing, Transwell, caspase-3 activity, and western blot assays. TGF-ß1 treatment enhanced ovarian cancer cell epithelial-mesenchymal transition (EMT), whereas sorafenib and a selective TGF-ß1 inhibitor Ly2157299 reversed tumor cell EMT, invasion, and expression of EMT markers (E-cadherin and vimentin). Sorafenib and Ly2157299 treatment also significantly reduced the tumor cell viability. Furthermore, both sorafenib and Ly2157299 significantly enhanced ovarian cancer cell radiosensitivity, as assessed by a caspase-3 activity assay. In conclusion, sorafenib inhibited ovarian cancer cell proliferation and mobility and induced tumor cell radiosensitivity. Molecularly, sorafenib could inhibit the TGF-ß1-mediated EMT. Future studies will assess sorafenib anti-ovarian cancer activity plus TGF-ß1 inhibitors in ovarian cancer in vivo.

Efficacy of Disitamab Vedotin in Treating HER2 2+/FISH- Gastric Cancer.

Currently, effective therapies for advanced gastric cancer with systemic metastasis are lacking. Pharmacological research has been slowly progressing over the past decades. Here, we report the case of a 56-year-old female with human epidermal growth factor receptor 2 (HER2) expression (IHC 2+/FISH-) in gastric cancer with systemic metastasis. The first-line therapeutic regime consisted of systemic administration of camrelizumab, local arterial infusion of oxaliplatin and arterial embolization, oral apatinib, and PS scheme (oral tegafur-gimeracil-oteracil (S-1) and paclitaxel (PTX), which was administered both intraperitoneally and systemically). After the treatment, a 3-month progression-free survival (PFS) was observed. Due to the occurrence of CTCAE grade 4 adverse reactions, the patient could not tolerate chemotherapy. In the second line of treatment, we replaced the PS scheme with disitamab vedotin and continued the use of carrilizumab and apatinib. After four cycles, efficacy evaluation showed that it was stable disease (SD), only CTCAE 1/2 grade adverse reactions occurred, and endoscopy examination showed local tumor control with a reduction in the ulcer lesion. At the time of submission of the current manuscript, a 6-month PFS was achieved and the treatment was continued. Due to the safety and efficacy of disitamab vedotin observed in our case, we propose that disitamab vedotin could be a promising drug for the treatment of advanced gastric cancer patients with HER2 expression.

A GRU-Based Method for Predicting Intention of Aerial Targets.

Since a target's operational intention in air combat is realized by a series of tactical maneuvers, its state presents the characteristics of temporal and dynamic changes. Depending only on a single moment to take inference, the traditional combat intention recognition method is neither scientific nor effective enough. Based on a gated recurrent unit (GRU), a bidirectional propagation mechanism and attention mechanism are introduced in a proposed aerial target combat intention recognition method. The proposed method constructs an air combat intention characteristic set through a hierarchical approach, encodes into numeric time-series characteristics, and encapsulates domain expert knowledge and experience in labels. It uses a bidirectional gated recurrent units (BiGRU) network for deep learning of air combat characteristics and adaptively assigns characteristic weights using an attention mechanism to improve the accuracy of aerial target combat intention recognition. In order to further shorten the time for intention recognition and with a certain predictive effect, an air combat characteristic prediction module is introduced before intention recognition to establish the mapping relationship between predicted characteristics and combat intention types. Simulation experiments show that the proposed model can predict enemy aerial target combat intention one sampling point ahead of time based on 89.7% intent recognition accuracy, which has reference value and theoretical significance for assisting decision-making in real-time intention recognition.

Circ_0006404 Accelerates Prostate Cancer Progression Through Regulating miR-1299/CFL2 Signaling.

BACKGROUND: Circular RNAs (circRNAs) have been proven to function as pivotal regulators in cancer occurrence and progression. However, the function of circ_0006404 (circRNA Forkhead box O3 (circFOXO3)in prostate cancer (PCa) is poorly understood. METHODS: The enrichment of circ_0006404, FOXO3, microRNA-1299 (miR-1299) and cofilin 2 (CFL2) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The viability, metastasis and proliferation were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, transwell and colony formation assays, respectively. Flow cytometry was used to assess cell cycle progression and apoptosis. Circ_0006404/miRNAs interactions were explored using Circular RNA Interactome database, while TargetScan software was used for seeking the targets of miR-1299. Dual-luciferase reporter assay, RNA-pull down and RNA immunoprecipitation (RIP) assays were conducted to verify the target interaction between miR-1299 and circ_0006404 or CFL2. CFL2 protein level was analyzed by Western blot assay. Animal experiments were performed to test the role of circ_0006404 in PCa tumor growth in vivo. RESULTS: Circ_0006404 level was notably elevated in PCa. Circ_0006404 contributed to the viability, metastasis and proliferation and impaired the apoptosis of PCa cells. Circ_0006404 directly targeted miR-1299, and miR-1299 silencing largely reversed circ_0006404 interference-induced influences in PCa cells. CFL2 directly bound to miR-1299, and miR-1299-induced effects in PCa cells were largely attenuated by CFL2 overexpression. CFL2 was regulated by circ_0006404/miR-1299 axis in PCa cells. Circ_0006404 promoted PCa progression via miR-1299/CFL2 axis in vivo. CONCLUSION: Circ_0006404 accelerated the survival, motility and proliferation while impeded the apoptosis of PCa cells via miR-1299/CFL2 axis. Circ_0006404 might be a stable potential bio-marker for PCa diagnosis and treatment.

Curcumin inhibits the growth of triple-negative breast cancer cells by silencing EZH2 and restoring DLC1 expression.

Enhancer of zeste homolog 2 (EZH2), an oncogene, is a commonly up-regulated epigenetic factor in human cancer. Hepatocellular carcinoma deletion gene 1 (DLC1) is an antioncogene that is either expressed at low levels or not expressed in many malignant tumours. Curcumin is a promising anticancer drug that has antitumour effects in many tumours, but its mechanism of action is unclear. Our research demonstrated that EZH2 was up-regulated in breast cancer (BC) tissues and cells, whereas DLC1 was down-regulated, and the expression of EZH2 and DLC1 was negatively correlated in BC. By analysing the characteristics of clinical cases, we found that positive expression of EZH2 and negative expression of DLC1 may be predictors of poor prognosis in patients with triple-negative breast cancer (TNBC). Moreover, knockdown of EZH2 expression restored the expression of DLC1 and inhibited the migration, invasion and proliferation, promoted the apoptosis, and blocked the cell cycle of MDA-MB-231 cells. Furthermore, we found that curcumin restored the expression of DLC1 by inhibiting EZH2; it also inhibited the migration, invasion and proliferation of MDA-MB-231 cells, promoted their apoptosis and blocked the cell cycle. Finally, xenograft tumour models were used to demonstrate that curcumin restored DLC1 expression by inhibiting EZH2 and also inhibited the growth and promoted the apoptosis of TNBC cells. In conclusion, our results suggest that curcumin can inhibit the migration, invasion and proliferation, promote the apoptosis, block the cycle of TNBC cells and restore the expression of DLC1 by inhibiting the expression of EZH2.

Upregulated Circular RNA circ-UBE2D2 Predicts Poor Prognosis and Promotes Breast Cancer Progression by Sponging miR-1236 and miR-1287.

Emerging evidence suggests that circular RNAs (circRNAs) are linked to the development and progression of human cancers. Nevertheless, their contribution to breast cancer (BC) is still largely unknown. In the current study, we screened and identified a novel circRNA, circ-UBE2D2, which was highly expressed in BC cell lines and tissues and was closely related to aggressive clinical features and dismal prognosis. Small interfering RNA (siRNA)-mediated circ-UBE2D2 silencing notably inhibited the proliferation, migration and invasion of BC cells, whereas circ-UBE2D2 overexpression displayed opposite effects. Mechanistically, circ-UBE2D2 was able to simultaneously function as molecular sponges of miR-1236 and miR-1287 to regulate the expression of their respective target genes. Moreover, circ-UBE2D2-induced tumor-promoting effects could be effectively blocked by miR-1236 or miR-1287 in BC cells. More importantly, therapeutic delivery of cholesterol-conjugated si-circ-UBE2D2 oligonucleotides significantly delayed tumor growth in vivo. Overall, our findings indicate that circ-UBE2D2 plays an essential oncogenic role in BC, and targeting circ-UBE2D2 may be a feasible treatment for BC patients.

Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer.

OBJECTIVE: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. METHODS: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis. RESULTS: After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors' clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). CONCLUSIONS: NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

LncRNA NRON down-regulates lncRNA snaR and inhibits cancer cell proliferation in TNBC.

NRON mediates the degradation of tat protein to participate in HIV-1 infection. Interestingly, our study observed the down-regulation of NRON in triple-negative breast cancer (TNBC) tissues compared with paired adjacent healthy tissues. In contrast, lncRNA snaR was up-regulated in TNBC tissues and was inversely correlated with NRON. Expression levels of snaR increased, while expression levels of NRON decreased along with the increase of clinical stages. The snaR overexpression resulted in promoted cancer cell proliferation but did not significantly affect NRON expression. NRON overexpression inhibited cancer cell proliferation and down-regulated snaR. The snaR overexpression reduced the effects of NRON overexpression. We therefore conclude that NRON may down-regulate lncRNA snaR to inhibit cancer cell proliferation in TNBC.

miR-106b promotes cell invasion and metastasis via PTEN mediated EMT in ESCC.

MicroRNA (miR)-106b serves an essential function in a variety of human cancer types, particularly in the process of invasion and metastasis. However, the function and mechanism of miR-106b in the invasion and metastasis of esophageal squamous cell carcinoma (ESCC) has remained elusive. In the present study, it was demonstrated that miR-106b was upregulated in ESCC tissues and cell lines. Furthermore, miR-106b expression in ESCC tissues was positively associated with lymphatic metastasis. Inhibition of miR-106b in EC-1 and EC9706 cells decreased not only the invasion and metastasis ability but also the proliferation ability of EC-1 and EC9706 cells. In addition, miR-106b had the ability to induce epithelial-to-mesenchymal transition (EMT) in EC-1 and EC9706 cells. In terms of the underlying mechanism, it was revealed that miR-106b promoted the invasion, metastasis and proliferation ability of EC-1 and EC9706 cells by directly targeting phosphatase and tension homolog (PTEN). Furthermore, miR-106b induced EMT in EC-1 and EC9706 cells by suppressing the expression of PTEN. In summary, the present study revealed that miR-106b contributed to invasion and metastasis in ESCC by regulating PTEN mediated EMT. Downregulation of miR-106b may be a novel strategy for preventing tumor invasion and metastasis.

Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells.

Previous studies have demonstrated that Licochalcone A possesses anti-inflammatory, anticancer, anti-bacterial, anti-malarial and anti-parasitic activities. In the present study the potential anticancer effects of Licochalcone A on MCF-7 cells were investigated. Licochalcone A significantly decreased cell viability and promoted autophagy and apoptosis, as demonstrated by an MTT assay, acridine orange staining and Annexin V-fluorescein isothiocyanate staining, respectively. Western blot analyses demonstrated that Licochalcone A treatment activated the LC3-II signaling pathway while suppressing the phosphoinositide 3-kinase (PI3K)/RAC-α serine-threonine-protein kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. In addition, Licochalcone A significantly increased caspase-3 activity and significantly decreased B-cell lymphoma-2 expression. The results from the present study indicate that Licochalcone A inhibits PI3K/Akt/mTOR activation, and promotes autophagy and apoptosis in MCF-7 cells.

Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies.

OBJECTIVES: The objective of this study was to evaluate the association between metformin therapy and the incidence of gastric cancer (GC) in patients with type 2 diabetes mellitus (T2DM). METHODS: We systemically searched the following databases for studies published between the databases' dates of inception and Nov. 2016: PubMed, Embase, the Cochrane Library, the Web of Science, and the China National Knowledge Infrastructure (CNKI). Hazard ratios (HR)and corresponding 95% confidence intervals (CIs) for the association between metformin therapy and the incidence of GC in patients with T2DM were the outcome measures assessed in this study. STATA 12.0 (Stata Corporation, College Station, Texas, USA) was used to conduct the statistical analysis. RESULTS: A total of seven cohort studies including 591,077 patients met all the criteria for inclusion in the analysis. Our data showed that metformin therapy was associated with a significantly lower incidence of GC in patients with T2DM than other types of therapy (HR=0.763, 95% CI: 0.642˜0.905). Subgroup analysis showed that patients living in Taiwan benefitted more from metformin therapy than patients living in any other region, as metformin significantly decreased the risk of GC in patients living in Taiwan but did not significantly decrease the risk of GC in patients living in other regions (HR=0.514, 95% CI: 0.384-0.688). The results of the present analysis support the idea that metformin facilitates reductions in the risk of T2DM-related GC. CONCLUSIONS: The risk of GC among patients with T2DM is lower in patients receiving metformin therapy than in patients not receiving metformin therapy.

HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma­not otherwise specified.

Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma­not otherwise specified (IDC­NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC­NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC­NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC­NOS were detected using immunohistochemistry, western blotting and reverse transcription­quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1­positive, and 100 out of 148 (67.6%) were ER­positive. Of the latter, 28% (28/100) were HPK1­positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=­0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC­NOS tissues were PR­ or HER2­positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor­node­metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER­positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC­NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC­NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.

Metformin inhibited esophageal squamous cell carcinoma proliferation in vitro and in vivo and enhanced the anti-cancer effect of cisplatin.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied. In the present study, we found that metformin exhibited not only an anti-proliferation ability in a dose and time dependent manner but also a proapoptosis effect in a dose dependent manner in ESCC cell line KYSE450. Our in vivo experiment also showed that metformin markedly inhibited KYSE450 xenograft tumors growth compared to those treated with normal saline. What's more, no obvious toxic reactions were observed. To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo. During the therapy of cancer, in order to overcome side effects, combination therapy was often used. In this paper, we demonstrated that metformin potentiated the effects of cisplatin via inhibiting cell proliferation and promoting cell apoptosis. Taken together, metformin owned the potential anti-cancer effect on ESCC in monotherapy or was combined with cisplatin and these results laid solid basis for the use of metformin in ESCC.

Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma.

Cancer stem cells (CSCs) are defined as a rare subpopulation of undifferentiated cells with biological characteristics that include the capacity for self-renewal, differentiation into various lineages, and tumor initiation. To explore the mechanism of CSCs in esophageal squamous cell carcinoma (ESCC), we focused on Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a target gene of the Wnt signaling pathway, which has been identified as a marker of intestinal stem cells and shown to be overexpressed in several human malignancies. Lgr5 expression was significantly correlated with lymph node metastasis, increased depth of invasion, increased tumor size, advanced differentiation, higher AJCC stage and poorer survival. Silencing of Lgr5 expression in the ESCC cell line KYSE450 by small interfering RNA (siRNA) strongly inhibited cell proliferation, migration and invasion ability, the expression of CSCs-related genes and Wnt/ß-catenin signaling. In addition, Lgr5 was highly expressed in ESCC spheroid body cells, which were identified by high expression of CSCs-related genes, and high tumorigenicity in vivo. Taken together, these results demonstrate that Lgr5 activation of Wnt/ß-catenin signaling is a potential mechanism to promote the progression of ESCC and ESCC stem cell renewal, and Lgr5 may be used as a molecular target for the development of treatments for ESCC.

miR-4417 Targets Tripartite Motif-Containing 35 (TRIM35) and Regulates Pyruvate Kinase Muscle 2 (PKM2) Phosphorylation to Promote Proliferation and Suppress Apoptosis in Hepatocellular Carcinoma Cells.

BACKGROUND MicroRNAs (miRNAs) are a class of small non-coding RNAs that are strongly involved in various types of carcinogenesis, including hepatocellular carcinoma (HCC). This study aimed to clarify whether miR-4417 promotes HCC growth by targeting TRIM35 and regulating PKM2 phosphorylation. MATERIAL AND METHODS Online software, including TargetScan and miRanda, was used to predict the potential target of miR-4417. Real-Time PCR (qRT-PCR) and Western blot assays were performed to detect the expression levels of mRNA and protein, respectively. Cell proliferation was measured by MTT assay and apoptosis in A549 cells was examined by flow cytometry. RESULTS Bioinformatics reveal that TRIM35 mRNA contains 1 conserved target site of miR-4417. High level of miR-4417 and low levels of TRIM35 mRNA and protein were observed in HCC cells compared with a normal liver cell line. Biological function analysis showed that miR-4417 inhibitor inhibits cell proliferation and promotes apoptosis in HCC cells. Furthermore, we verified that TRIM35 is a functional target of miR-4417 by use of luciferase reporter assay, and TRIM35 overexpressing showed an elevation of proliferation and a reduction of apoptosis in HCC cells. We subsequently investigated whether miR-4417 and TRIM35 regulate HCC cell proliferation and apoptosis through PKM2 Y105 phosphorylation, and the results supported our speculation that miR-4417 targets TRIM35 and regulates the Y105 phosphorylation of PKM2 to promote hepatocarcinogenesis. CONCLUSIONS Our findings indicate that miR-4417 may function as an oncogene in HCC and is a potential alternative therapeutic target for this deadly disease.

TM4SF1 promotes the self-renewal of esophageal cancer stem-like cells and is regulated by miR-141.

Cancer stem-like cells have been identified in primary human tumors and cancer cell lines. Previously we found TM4SF1 gene was highly expressed in side population (SP) cells from esophageal squamous cell carcinoma (ESCC) cell lines, but the role and underlying mechanism of TM4SF1 in ESCC remain unclear. In this study, we observed TM4SF1 was up-regulated but miR-141 was down-regulated in SP cells isolated from ESCC cell lines. TM4SF1 could stimulate the self-renewal ability and carcinogenicity of esophageal cancer stem-like cells, and promote cell invasion and migration. In miR-141 overexpression cells, the expression of TM4SF1 was significantly reduced. We also found that overexpression of miR-141 could abolish the self-renewal ability and carcinogenicity of esophageal cancer stem-like cells and decrease cell invasion and migration by suppressing TM4SF1. Consequently, TM4SF1 is a direct target gene of miR-141. The regulation of TM4SF1 by miR-141 may play an important role in controlling self-renewals of esophageal cancer stem-like cells. It may also promote the development of new therapeutic strategies and efficient drugs to target ESCC stem-like cells.

MiR-424-5p participates in esophageal squamous cell carcinoma invasion and metastasis via SMAD7 pathway mediated EMT.

BACKGROUNDS: ESCC is a life-threatening disease due to invasion and metastasis in the early stage. Great efforts had been made to detect the molecular mechanisms which led to the invasion and metastasis in ESCC. Recent evidence had suggested that deregulation of miR-424-5p took an important role in cancers. However, its role and functional mechanism in ESCC had seldom been elucidated. METHODS: The expression levels of miR-424-5p were detected in ESCC tissues and cell lines by real-time PCR methods. Then, the invasion, metastasis and proliferation ability of ESCC cell lines transfected with miR-424-5p mimics were analyzed separately by transwell invasion assay, wound healing assay and cell proliferation assay. Finally, the target gene of miR-424-5p was studied and verified by luciferase activity assay. And the role of miR-424-5p in EMT was also investigated by real-time PCR and western blot assay. RESULTS: We showed that the expression levels of miR-424-5p were decreased both in ESCC tissues and cell lines. Furthermore, the expression levels of miR-424-5p were negatively linked to lymph node metastasis in ESCC tissues. Restoration of miR-424-5p in EC-1 cells by using miR-424-5p mimics could decrease the invasion, metastasis and proliferation of EC-1 cells, indicating its role in inhibition on the invasion and metastasis ability of ESCC cells and tissues. In addition, we demonstrated that SMAD7 was a specific target gene for miR-424-5p by luciferase activity assay and miR-424-5p could not only negatively regulate SMAD7 expression but also participate in EMT via SMAD7, because overexpression of SMAD7 could partly enhance the miR-424-5p anti-EMT function. CONCLUSIONS: Our results described that miR-424-5p -SMAD7 pathway contributed to ESCC invasion and metastasis and up-regulation of miR-424-5p perhaps provided a strategy for preventing tumor invasion, metastasis.