Retraction Note: Mir-655 up-regulation suppresses cell invasion by targeting pituitary tumor-transforming gene-1 in esophageal squamous cell carcinoma.

The Editor-in-Chief has retracted this article [1] because Figure 3a overlaps with Figure 2 in [2]. An investigation by Zhengzhou University has confirmed this. The data reported in this article are therefore unreliable. There is also considerable text overlap with a previously published article [3]. Guoqiang Zhao does not agree with this retraction. The other authors have not responded to correspondence from the editor about this retraction.

Retraction Note: miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer.

The Editor-in-Chief has retracted this article [1] because Figure 6b overlaps with Figure 8 of [2] and Figure 4a overlaps with Figure 2b of [3].

Retraction Note: Overexpression of A613T and G462T variants of DNA polymerase ß weakens chemotherapy sensitivity in esophageal cancer cell lines.

[This retracts the article DOI: 10.1186/s12935-016-0362-x.].

Retraction Note to: Effect of miR-451 on the Biological Behavior of the Esophageal Carcinoma Cell Line EC9706.

The Editor-in-Chief has retracted this article [1] because Figure 8 overlaps with Figure 6b of [2] and Figure 6 overlaps with Figure 3 of [3] and Figure 3 of [4].

MiR-149 sensitizes esophageal cancer cell lines to cisplatin by targeting DNA polymerase ß.

Human DNA polymerase ß (polß) is a small, monomeric protein essential for short-patch base excision repair (BER). polß plays an important role in the regulation of chemotherapy sensitivity in tumour cells. In this study, we determined that the expression levels of polß mRNA and miR-149 in tumour tissues were significantly higher than in adjacent non-tumour tissues. We also found that the expression level of miR-149 in EC tumour tissues was inverse to that of polß expression. Bioinformatics analysis and dual-luciferase reporter assay predicted that miR-149 negatively regulates polß expression by directly binding to its 3'UTR. CCK-8 assay indicated that miR-149 could enhance the anti-proliferative effects of cisplatin in EC1 and EC9706 cell lines. Flow cytometry, caspase 3/7 activity, and immunofluorescence microscopy results indicated that miR-149 could enhance the apoptotic effects of cisplatin in EC1 and EC9706 cell lines. We also showed that the expression of polß lacking the 3'UTR sequence could override the proliferative and apoptotic functions of miR-149, suggesting that miR-149 negatively regulates polß expression by binding to its 3'UTR. Surface plasmon resonance results also showed that miR-149 could bind with wild-type polß. In addition, we identified a new variant of polß (C1134G). In conclusion, this study confirms that miR-149 may enhance the sensitivity of EC cell lines to cisplatin by targeting polß, and that miR-149 may be unable to regulate the C1134G variant of polß. Based on these findings, potential drugs could be developed with a focus on enhanced sensitivity of EC patients to chemotherapy.

RETRACTED: The long noncoding RNA CASC2 inhibits tumorigenesis through modulating the expression of PTEN by targeting miR-18a-5p in esophageal carcinoma.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. In the article Figure 3A top and center panel are duplicated and in Figure 5A elements are duplicated from previous publications from the same authors in Tumor Biol. (2014) 35:12583­12592 DOI 10.1007/s13277-014-2579-4 (Figure 3) and Dig Dis Sci (2013) 58:706­714 DOI 10.1007/s10620-012-2395-x (Figure 8). The authors recognize mishandling of these images which affects the validation of the study and would like to apologize to readers.

microRNA-186 inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma by targeting SKP2.

miR-186 has been demonstrated to have a significant role as a tumor suppressor in many types of cancers. Nevertheless, its biological function in esophageal squamous cell carcinoma (ESCC) remains unknown. In the present study, we found that the expression level of miR-186 was downregulated in ESCC in comparison with the adjacent normal tissues and was significantly associated with differentiation level, TNM stage, and lymph node metastasis of ESCC. Functional experiments revealed that enforced overexpression of miR-186 in ESCC cells suppressed the proliferation, invasion, and induced the apoptosis of cells. Luciferase reporter assay and western blotting analysis were performed to verify the target gene regulated by miR-186, SKP2. Our findings established that the miR-186 has a suppressive role in ESCC progression via SKP2-mediated pathway, and this implies that miR-186 could be a potential therapeutic target for ESCC.

α-Solanine Modulates the Radiosensitivity of Esophageal Cancer Cells by Inducing MicroRNA 138 Expression.

BACKGROUND: Esophageal cancer (EC) is one of the most common malignant tumors in the world. Due to difficulties with performing the operation, most patients choose to have palliative treatment instead. Radiotherapy is one of the main palliative treatments of EC. However, the clinical efficacy of radiotherapy is not satisfactory α-Solanine is a bioactive component of steroidal glycoalkaloids which has been demonstrated to exhibit anti-metastasis activity in different cancers. In the present study, we determined the effect of α-solanine on the radiosensitivity of EC cells and priliminarily explored the underlying molecular mechanisms. METHODS: Cell Counting Kit-8 (CCK-8) assay was conducted to found the cytotoxic effect of α-solanine on EC cells. CCK-8 assay and colony-forming survival assays were performed to explore the effect of α-solanine on cell viability and proliferation of EC cells after irradiation. Immunofluorescence and comet assays were used to detect the effect of α-solanine on DNA repair capacity of EC cells after irradiation. The flow cytometry (FCM) and Hoechst/PI staining were conductd to study the effect of α-solanine on apoptosis of EC cells after irradiation. RESULTS: The cytotoxic effect of α-solanine to EC cells was dose-dependent. The results of CCK-8, colony-forming survival assay, immunofluorescence, comet assay, FCM and Hoechst/PI staining showed that α-solanine could enhance the radiosensitivity of EC cells. α-Solanine could downregulate Survivin expression level by upregulating miR-138 expression in EC cells. Upregulation of miR-138 and knock down Survivin both enhanced the radiosensitivity of EC cells. Moreover, Survivin could restore the effect of α-solanine and miR-138 on radiosensitivity of EC cells. CONCLUSIONS: α-solanine could enhance the radiosensitivity of esophageal cancer cells by inducing microRNA-138 expression, and probably be an effective radiosensitizer in treating EC.

Curcumin inhibits cell growth and induces cell apoptosis through upregulation of miR-33b in gastric cancer.

In this work, the in vitro experiments about biological mechanisms of curcumin were conducted using the gastric cancer cell lines SGC-7901 and BGC-823. After 24-h exposure to curcumin at the concentrations of 5, 10, 15, 20, and 40 µmol/L, two cells showed the decreased proliferation and increased apoptosis abilities. Real-time PCR, Cell Counting Kit-8 (CCK-8) assay, western blotting, and cell apoptosis assay were used to further study the underlying mechanisms of curcumin. The first stage of our studies showed that curcumin affected the expression of miR-33b, which, in turn, affected the expression of the X-linked inhibitor of apoptosis protein (XIAP) messenger RNA (mRNA). Next, curcumin was also identified to regulate the proliferation and apoptosis of SGC-7901 and BGC-823 cells. Further bioinformatics analysis and luciferase reporter assays proved that XIAP was one of the target genes of miR-33b. In the next stage, SGC-7901 and BGC-823 cells were treated with 20 µL curcumin, miR-33b mimics, and small interfering RNA (siRNA) of XIAP, respectively. The results showed that curcumin had similar effects on cell growth and apoptosis as the upregulation of miR-33b and the upregulation of the siRNA of XIAP. The results that followed from the restore experiments showed that curcumin affected cell growth and apoptosis presumably by upregulating the XIAP targeting in gastric cancer. Collectively, our results indicate that curcumin-miR-33b-XIAP coupling might be an important mechanism by which curcumin induces the apoptosis of SGC-7901 and BGC-823 cells.

G648C variant of DNA polymerase ß sensitizes esophageal cancer to chemotherapy.

Human DNA polymerase ß (polß) is a small monomeric protein that is essential for short-patch base excision repair. It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. We have previously identified a G to C point mutation at nucleotide 648 (G648C) of polß in esophageal cancer (EC). In this study, we evaluated the mutation of polß in a larger cohort of EC patients by RT-PCR and sequencing analysis. The function of the mutation was evaluated by MTT, in vivo tumor growth, and flow cytometry assays. The G648C mutation occurred in 15 (3.45 %) of 435 EC patients. In addition, patients with this mutation had significantly longer survival time than those without, following postoperative chemotherapy. Cell lines with G648C mutation in polß gene were more sensitive to treatment with 5-fluorouracil and cisplatin than those with wild-type polß. These results suggest that polß gene with G648C mutation in surgically resected esophagus may be clinically useful for predicting responsiveness to chemotherapy in patients with EC. The polß gene alteration may serve as a prognostic biomarker for EC.

Overexpression of A613T and G462T variants of DNA polymerase ß weakens chemotherapy sensitivity in esophageal cancer cell lines.

BACKGROUND: Human DNA polymerase ß (polß) is a small monomeric protein that is essential for short-patch base excision repair. It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. METHODS: We evaluated the mutation of polß in a larger cohort of esophageal cancer (EC) patients by RT-PCR and sequencing analysis. The function of the mutation was evaluated by CCK-8, in vivo tumor growth, and flow cytometry assays. RESULTS: There are 229 patients with the polß mutation, 18 patients with A613T mutation, 12 patients with G462T mutation among 538 ECs. Analysis results of survival time showed that EC patients with A613T, G462T mutation had a shorter survival than the others (P < 0.05). CCK-8 and flow cytometry assays results showed the A613T, G462T EC9706 cells were less sensitive than WT cells to 5-FU and cisplatin (P < 0.05). Experiments results in vivo showed that the tumor sizes of A613T and G462T group were larger than WT and polß-/- groups (P < 0.05). CONCLUSIONS: In this study, we discovered A to T point mutation at nucleotide 613 (A613T) and G to T point mutation at nucleotide 462 (G462T) in the polß gene through 538 EC patients cohort study. A613T and G462T variant of DNA polymerase ß weaken chemotherapy sensitivity of esophageal cancer.

miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer.

BACKGROUND: miR-663 is associated with many important biologic processes, such as the evolution, development, viral infection, inflammatory response, and carcinogenesis among vertebrates. However, the molecular function and mechanism of miR-663 in pancreatic cancer growth and invasion is still unclear. METHODS: Western blot and real-time PCR were used to study the expression level of eEF1A2 protein and miR-663 in pancreatic cancer tissues and cell lines. The Pearson χ (2) test was used to determine the correlation between miR-663 expression and clinicopathologic features of patients. Patients' survival was analyzed using the Kaplan-Meier method, using the log-rank test for comparison. The biological function of miR-663 was examined by measuring cell growth, cell invasion and apoptosis analysis in vitro and in vivo. miR-663 target gene and signaling pathway was identified by luciferase activity assay and western blot. RESULTS: We found that, in pancreatic cancer, eEF1A2 was significantly upregulated but miR-663 was significantly downregulated. Further results showed that the expression level of eEF1A2 and miR-663 was strongly associated with TNM stage and node metastasis status of the patients. miR-663 and eEF1A2 were inversely correlated with each other, and the changes in the expression levels of each can also predict the survival of patients with pancreatic cancer. We identified miR-663 as a tumor attenuate molecular that attenuated the proliferation and invasion of pancreatic cancer cells both in vitro and in vivo. Finally, we confirmed that the expression of eEF1A2 can partially restore the pro-apoptotic and anti-invasion functions of miR-663. CONCLUSIONS: miR-663 attenuated the proliferation and invasion of pancreatic cells both in vitro and in vivo by directly targeting eEF1A2. miR-663 and eEF1A2 might be potential targets for the treatment of pancreatic cancer in the future.

MiR-499 Enhances the Cisplatin Sensitivity of Esophageal Carcinoma Cell Lines by Targeting DNA Polymerase ß.

BACKGROUND: Human DNA polymerase ß (DNA polymerase ß, polß) is a small monomeric protein essential for short-patch base excision repair (BER). It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. METHODS: Luciferase reporter and western blot assays were used to determine whether polß is a major target of miR-499. CCK-8, colony-forming survival and in vivo tumor growth assays were conducted to evaluate if miR- 499 can potentially enhance the cisplatin sensitivity and therefore inhibit the proliferation of esophageal cancer (EC) cells. Flow cytometry and immunofluorescence microscopy assays were performed to evaluate whether miR-499 enhance the cisplatin sensitivity and the corresponding apoptosis in EC cells. RESULTS: polß was pinpointed as a target gene of miR- 499. Additionally, we identified that miR-499 can enhance cisplatin's function of inhibiting proliferation and of promoting apoptosis in EC9706 and KYSE30 cell lines. CONCLUSIONS: We first investigated whether miR-499 modulates polß, and observed the influence of miR-499 up-regulation on the sensitivity of EC cell lines to cisplatin treatment. Our study paves the way for more insightful understanding and application of chemotherapy in esophageal cancer in the future.

MiR-144 inhibits proliferation and induces apoptosis and autophagy in lung cancer cells by targeting TIGAR.

BACKGROUND: MiRNAs are noncoding RNAs of 20-24 nucleotides that function as post-transcriptional negative regulators of gene expression. MiRNA genes are usually transcribed by RNA polymerase II in the nucleus. Their initial products are pre-miRNAs which have cap sequences and polyA tails. The p53-induced glycolysis and apoptosis regulator (TIGAR) was discovered through microarray analysis of gene expression following activation of p53. However, little is known about the effect of miR-144 on cell proliferation and apoptosis and how it interacts with TIGAR. METHODS: We performed real-time PCR, western blotting, CCK8, colony formation, tumor growth, flow cytometry, Caspase3/7 activity, Hoechst 33342 staining, MDC staining of autophagic cells and luciferase reporter assays to detect the influence of miR-144 to lung cancer cells. RESULTS: miR-144 targeted TIGAR, inhibited proliferation, enhanced apoptosis, and increased autophagy in A549 and H460 cells. CONCLUSIONS: Our study improves our understanding of the mechanisms underlying lung cancer pathogenesis and may promote the development of novel targeted therapies.

miR-194 targets RBX1 gene to modulate proliferation and migration of gastric cancer cells.

RING box protein1 (RBX1), an essential component of SCF E3 ubiquitin ligases, plays an important role in gastric cancer. In the study, miR-194 and RBX1 expression was evaluated in 76 pairs of gastric tumor and non-tumor tissue samples by qRT-PCR, and clinicopathological characteristics were analyzed. CCK8, transwell assay, wound healing assay, and flow cytometry assay were performed to evaluate the effect of miR-194 on gastric cancer (GC) cellular proliferation, invasion, migration, apoptosis, and cell cycle, respectively. Luciferase reporter assays and Western blotting were used to evaluate whether RBX1 is a direct target of miR-194. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between miR-194 or RBX1 expression and patient survival. Then, we found that miR-194 was significantly downregulated and RBX1 upregulated in GC tissues; both of which showed significant association with tumor size, location, invasion, and tumor node metastasis. Cell proliferation, invasion, and migration were significantly restricted with miR-194 overexpression. miR-194 downregulated RBX1 protein expression, and luciferase assays showed that binding sites in the RBX1 3'UTR were required for miR-194-mediated repression of RBX1, indicating that RBX1 was a direct target of miR-194. Transfection of RBX1 without the 3'UTR restored the miR-194-inhibiting migration function. miR-194 overexpression or RBX1 lowexpression was associated with prolonged survival of GC patients. In conclusion, upregulation of miR-194 can inhibit proliferation, migration, and invasion of GC cells, possibly by targeting RBX1. Aberrant expression of miR-194 and RBX1 is correlated to GC patient survival time.

microRNA-30b inhibits cell invasion and migration through targeting collagen triple helix repeat containing 1 in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the largest histological subgroup of lung cancer and has increased in prevalence in China over the past 5 years. The 5-year survival rate has remained at 15-20 %, with a median survival of 8-12 months. The tumorigenesis and progression of NSCLC is orchestrated by numerous oncogene and anti-oncogene mutations and insights into microRNA function have increased our understanding of the process. Here, we investigated the effects of miR-30b on NSCLC cell invasion and migration and explored the underlying molecular mechanisms involved. METHODS: Quantitative reverse transcription PCR, wound healing assay, trans-well assays, western blotting and dual luciferase assays were performed to investigate the molecular mechanisms of miR-30b in NSCLC cells. RESULTS: MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both were associated with tumor differentiation, TNM stage and lymph node metastases. Up-regulation of miR-30b restricted A549 and Calu-3 cell invasion and migration. Additionally, the expression of Cthrc1, matrix metalloproteinase-9 and matrix metalloproteinase-2 was reduced, while metallopeptidase inhibitor-1 expression increased. Bioinformatics analysis identified Cthrc1 as a target of miR-30b and western blotting and luciferase reporter assays confirmed that miR-30b regulates Cthrc1 by directly binding to its 3'UTR. Transfection of Cthrc1 without the 3'UTR restored the miR-30b inhibiting cell invasion. Up-regulation of miR-30b or down-regulation of Cthrc1 had potential significance in the invasion and metastasis of NSCLC. CONCLUSIONS: MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both of them were related to tumor differentiation, TNM stage and lymph node metastases. MiR-30b affected NSCLC cells invasion and migration by regulating Cthrc1.

Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAC), the primary histological type of non-small cell lung cancer (NSCLC), has displayed an increasing incidence and mortality worldwide. However, therapeutic approaches were limited. Dysregulation of some lncRNAs has been shown in various types of cancers including LAC. The aim of the present study was to vertify lncRNA DLX6-AS1 expression in LAC. METHODS: Microarray assay revealed expression profile of lncRNAs in LAC. qRT-PCR ( quantitative reverse transcription PCR) was performed to identify lncRNA DLX6-AS1 expression level in 72 paired LAC and adjacent normal lung tissues. qRT-PCR and Western blotting were used to verify that down-regulation lncRNA DLX6-AS1 decreased DLX6 (distal-less homeobox 6) mRNA and protein expression. RESULTS: Microarray analysis identified up-regulation of 272 lncRNAs and down-regulation of 635 lncRNAs in LAC tissues. The expression level of lncRNA DLX6-AS1 in LAC tissues was significantly higher compared to paired adjacent normal lung tissues (P< 0.05). In addition, its expression level was closed correlated with both histological differentiation (P = 0.004) and TNM stage (P = 0.033). qRT-PCR and Western blotting analysis showed that DLX6 mRNA and protein levels were lower in si-LncRNA group than in the NC (negative control) and Blank groups. CONCLUSIONS: Microarray analysis identified that lncRNA DLX6-AS1 was up-regulated in LAC tissues. High DLX6-AS1 expression levels were significantly associated with both histological differentiation and TNM stage. Down-regulation of lncRNA DLX6-AS1 expression decreased the DLX6 mRNA and protein levels.

Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells.

Myricetin is a flavonoid that is abundant in fruits and vegetables and has protective effects against cancer and diabetes. However, the mechanism of action of myricetin against gastric cancer (GC) is not fully understood. We researched myricetin on the proliferation, apoptosis, and cell cycle in GC HGC-27 and SGC7901 cells, to explore the underlying mechanism of action. Cell Counting Kit (CCK)-8 assay, Western blotting, cell cycle analysis, and apoptosis assay were used to evaluate the effects of myricetin on cell proliferation, apoptosis, and the cell cycle. To analyze the binding properties of ribosomal S6 kinase 2 (RSK2) with myricetin, surface plasmon resonance (SPR) analysis was performed. CCK8 assay showed that myricetin inhibited GC cell proliferation. Flow cytometry analysis showed that myricetin induces apoptosis and cell cycle arrest in GC cells. Western blotting indicated that myricetin influenced apoptosis and cell cycle arrest of GC cells by regulating related proteins. SPR analysis showed strong binding affinity of RSK2 and myricetin. Myricetin bound to RSK2, leading to increased expression of Mad1, and contributed to inhibition of HGC-27 and SGC7901 cell proliferation. Our results suggest the therapeutic potential of myricetin in GC.

BTG3 upregulation induces cell apoptosis and suppresses invasion in esophageal adenocarcinoma.

B cell translocation gene 3 (BTG3) is a tumor suppressor by inhibiting cell proliferation, migration, and regulating cell cycle progression in several tumors. However, its role in esophageal adenocarcinoma (EAC) remains unknown. Here, we detected the expression of BTG3 in EAC tissues and subsequent progression. BTG3 expression was significant decreased in EAC tissues and cell lines detected by real-time RT-PCR and Western blot. Relationships of BTG3 with EAC clinicopathology were analyzed statistically. The decrease expression of BTG3 is associated with lymph node metastases. In vitro assay demonstrated that overexpression of BTG3 significantly suppressed colony formation and proliferation of EAC cells. The suppressed migration and invasion abilities found in BTG3-overexpressing EAC cells. Our findings suggested that BTG3 is suppressor in the progression of EAC.

Upregulation of miR-494 Inhibits Cell Growth and Invasion and Induces Cell Apoptosis by Targeting Cleft Lip and Palate Transmembrane 1-Like in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Potential target genes of microRNA (miR)-494 have been reported in many types of cancers. However, the role of miR-494 in esophageal squamous cell carcinoma (ESCC) remains unknown. AIM: This study focused on the expression and biological function of miR-494 in ESCC. METHODS: Using bioinformatics analyses, we found that cleft lip and palate transmembrane 1-like (CLPTM1L) was a potential target of miR-494. We performed quantitative real-time (qRT) PCR assays in 37 ESCC tumor tissues to determine the expression of miR-494 and CLPTM1L mRNA, and we analyzed the correlation between both of these factors and clinical characteristics. The cell counting kit-8 and colony formation assays were used to evaluate the effects of miR-494 expression on the proliferation of ESCC cells. The transwell migration assay and flow cytometric apoptosis assay were performed to study the influence of miR-494 on the invasion and apoptosis of ESCC cells. Western blotting, luciferase assays, and CLPTM1L knockdown experiments were used to determine whether CLPTM1L was a target of miR-494. RESULTS: The qRT-PCR assays showed significant downregulation of miR-494 (P < 0.05) and upregulation of CLPTM1L mRNA (P < 0.05), both of which were significantly associated with lymph node metastases (P < 0.05). High expression of miR-494 inhibited cell proliferation and invasion and promoted cell apoptosis (P < 0.05). The results also showed that CLPTM1L was a target of miR-494. CONCLUSION: These results show that the expression of miR-494, which can regulate cell growth, invasion and apoptosis of ESCC cells by targeting CLPTM1L, is downregulated in ESCC tumor tissues. The miR-494-CLPTM1L pathway could be further exploited to develop a new approach to treat ESCC.