Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration.

Retraction of: 'Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration', by Tong Xu, Lunhua Huang, Zhiqiang Liu, Dongwen Ma, Guowei Zhang, Xiaofei Ning, Xinyang Lu, Hongsheng Liu, Biao Jiang JBUON 2019;24(2):686-692; PMID:31128024. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Diagnostic accuracy of ultrasonography for the prenatal diagnosis of esophageal atresia and tracheoesophageal fistula.

Ultrasound is recommended as a first-line requirement prior to MRI or amniotic fluid analysis, which have high diagnostic accuracy for esophageal atresia (EA). Therefore, the aim of the present prospective study was to evaluate the accuracy of high-performance ultrasound for the prenatal examination of EA/tracheoesophageal fistula (TOF). In total, 64 pregnant women with fetuses suspected of having EA/TOF participated in the study. The gestational age of the fetuses ranged between 16 and 40 weeks, with a mean of 26.33±3.57 weeks. Ultrasound images of the esophagus and trachea on parasternal and para-aortic axis longitudinal and transverse sections were compared with the results of standard postnatal diagnostic tests. Sensitivity and specificity values were determined and a receiver operating characteristic (ROC) curve was generated. Among all the fetuses screened, 16 were suspected of having EA/TOF during the prenatal ultrasonography. In postnatal examinations, 34 cases of EA/TOF were confirmed, corresponding to an EA/TOF incidence of 53.2% (95% CI, 40.2-65.7%). The area under the ROC curve (AUC) was lower for prenatal ultrasonography compared with postnatal diagnostic tests (AUC=0.55; 95% CI, 0.44-0.65). Considering postnatal examination as the gold standard, prenatal ultrasonography had a sensitivity of 29.4% (95% CI, 15.1-47.5%) and a specificity of 80% (95% CI, 61.4-92.3%) for the diagnosis of EA/TOF. In addition, the positive predictive value was 62.5% (95% CI, 35.4-82.8%), the negative predictive value was 50% (95% CI, 35.2-64.8%), the positive likelihood ratio was 1.47 (95% CI, 0.61-3.56) and the negative likelihood ratio was 0.88 (95% CI, 0.67-1.17). The results of the present study indicate that preoperative ultrasound has poor sensitivity but very good specificity for the diagnosis of EA/TOF. The use of ultrasound alone would result in a high rate of a false-positive diagnoses. However, prenatal ultrasonography may be useful as a preliminary screening tool to exclude patients for suspected EA/TOF.

Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration.

PURPOSE: Totarol is a plant-derived natural product and has been reported to exhibit important pharmacological activities. However, the anticancer activity of totarol has not been evaluated yet. Therefore, the present research work was designed to evaluate the antitumor effects of totarol in SGC-7901 human gastric cancer cells and human gastric epithelial mucosa cell line GES-1 (used as normal cell line model) together with examining its effects on induction of apoptosis, cell cycle phase distribution and cell migration. METHODS: The effect of totarol on cell cytotoxicity was evaluated by MTT cell viability assay. Inverted phase contrast microscopy was used to identify the effects on cell morphology, while transmission electron microscopy indicated the apoptosis-driven morphological changes in cancer cells. The effects on cell apoptosis were also evaluated by annexin V/PI staining, while cell cycle analysis was done by flow cytometry. In vitro wound healing assay estimated the effects of totarol on cell migration. RESULTS: The results indicated that totarol induced selective cytotoxic effects in SGC-7901 human gastric cancer cells concentration-dependently and exhibited lower toxicity in GES-1 normal cells. The totarol-treated cells showed significant alterations in cell morphology including rounding and cellular shrinkage. Untreated SGC-7901 cells exhibited normal cellular morphology with undamaged plasma membrane. However, treating cells with totarol led to damaged plasma membrane along with appearance of rounded protrusions (apoptotic bodies) containing damaged and broken chromatin material. Treatment with different doses of totarol led to profound suppression of wound healing. Totarol treatment also led to G2/M phase cell cycle arrest in these cells in a concentration-dependent manner. CONCLUSIONS: The present study indicated that totarol diterpene has the tendency to show selective anticancer effects in SGC-7901 human gastric cancer cells along with inducing apoptosis, cell cycle arrest and inhibition of cell migration.

Upregulated expression of MNX1-AS1 long noncoding RNA predicts poor prognosis in gastric cancer.

As important regulators of gene expression long noncoding RNAs (lncRNAs) are implicated in various physiological and pathological processes, including cancer. An oncogenic role of MNX1 antisense RNA 1 (MNX1-AS1) lncRNA has been suggested in cervical cancer and glioblastoma. In this study, we investigated the clinicopathological significance and biological function of MNX1-AS1 in gastric cancer (GC). The expression of MNX1-AS1 was analyzed by qRT-PCR in 96 GC and adjacent non-tumor tissues in relation to clinicopathological features and overall survival (OS) of patients, and in five human GC cell lines compared to a normal gastric epithelial cell line. Loss-of-function experiments using small interfering RNA (siRNA) targeting MNX1-AS1 (si-MNX1-AS1) were carried out in AGS and MGC-803 GC cell lines. Cell proliferation (CCK-8 assay), migration (Transwell) and invasion (Transwell Matrigel), and protein expression of proliferating cell nuclear antigen (PCNA), E-cadherin, N-cadherin, vimentin and matrix metallopeptidase 9 (MMP-9) were analyzed in transfected GC cells. Expression of MNX1-AS1 was significantly higher in GC vs. adjacent non-tumor tissues. Higher MNX1-AS1 expression was significantly associated with tumor size, TNM stage and lymph node metastasis. Kaplan-Meier analysis showed that GC patients with higher MNX1-AS1 expression had worse OS compared to patients with lower MNX1-AS1 expression. Multivariate analysis showed that MNX1-AS1 is an independent poor prognostic factor in GC. Knockdown of MNX1-AS1 significantly inhibited proliferation, migration and invasion of AGS and MGC-803 cells, and resulted in increased E-cadherin and decreased PCNA, N-cadherin, vimentin and MMP-9 expression. Taken together, these results suggest that MNX1-AS1 has an oncogenic function in GC and potential as a molecular target in GC therapy.

Ectopic Expression of miR-147 Inhibits Stem Cell Marker and Epithelial-Mesenchymal Transition (EMT)-Related Protein Expression in Colon Cancer Cells.

Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT) is a crucial step in tumor progression and is also involved in the acquisition of stem cell-like properties. Some miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here we investigated the role of miR-147 in the regulation of the stem cell-like traits of colon cancer cells. We observed that miR-147 was downregulated in several colon cancer cell lines, and overexpressed miR-147 decreased the expression of cancer stem cell (CSC) markers OCT4, SOX2, and NANOG in the colon cancer cell lines HCT116 and SW480. Overexpressed miR-147 inhibited EMT by increasing the expression of epithelial markers E-cadherin and α-catenin while decreasing the expression of mesenchymal markers fibronectin and vimentin. Moreover, activation of EMT by TGF-ß1 treatment significantly counteracted the inhibitive effect of miR-147 on the expression of CSC markers OCT4, SOX2, and NANOG, supporting the idea that overexpressing miR-147 inhibited stem cell-like traits by suppressing EMT in colon cancer. In addition, we found that overexpressed miR-147 downregulated the expression of ß-catenin, c-myc, and survivin, which were related to the Wnt/ß-catenin pathway. Moreover, treatment of miR-147 mimic-transfected cells with the Wnt/ß-catenin pathway activator LiCl attenuated the inhibitive effect of the miR-147 mimic on the EMT and stem cell-like traits of colon cancer cells, indicating that ectopic expression of miR-147 inhibited stem cell-like traits in colon cancer cells by suppressing EMT via the Wnt/ß-catenin pathway. In summary, our present study highlighted the crucial role of miR-147 in the inhibition of the stem cell-like traits of colon cancer cells and indicated that miR-147 could be a promising therapeutic target for colon cancer treatment.

[ARTICLE WITHDRAWN] Long Noncoding RNA LINC01296 Harbors miR-21a to Regulate Colon Carcinoma Proliferation and Invasion.

THIS ARTICLE WAS WITHDRAWN BY THE PUBLISHERS IN NOVEMBER 2020.

Exosomes Released by Gastric Cancer Cells Induce Transition of Pericytes Into Cancer-Associated Fibroblasts.

BACKGROUND Cancer-associated fibroblasts (CAFs) are functionally and structurally essential for tumor progression. There are 3 main origins of CAFs: mesenchymal stem cells (MSCs), epithelial-to-mesenchymal (EMT) transition cells, and tissue-resident cells. Pericytes retain characteristics of progenitor cells and can differentiate into other cells under normal physiological conditions and into myofibroblasts under pathological conditions. Exosomes play an important role in intercellular communication by transferring membrane components and nucleic acids between different cells. In this study, we evaluated whether cancer cell-derived exosomes are involved in regulating the transition of pericytes to CAFs. MATERIAL AND METHODS Exosomes from GES-1 and SGC7901 cells were isolated by serial centrifugation and purified from the supernatant by the 30% sucrose/D2O cushion method. A transmission electron microscope was used to observe exosome morphologies, and nanoparticle tracking analysis was used to analyze size distribution of exosomes. Western blot analysis, immunofluorescent staining, and qPCR were employed to detect CAFs marker expression and signaling pathways involved in CAFs transition. RESULTS Gastric cancer cell-derived exosomes enhanced pericytes proliferation and migration and induced the expression of CAFs marker in pericytes. We then demonstrated that the PI3K/AKT and MEK/ERK pathways were activated by tumor-derived exosomes, and BMP pathway inhibition reverses cancer exosomes-induced CAFs transition. CONCLUSIONS Our results suggest that gastric cancer cells induce the transition of pericytes to CAFs by exosomes-mediated BMP transfer and PI3K/AKT and MEK/ERK pathway activation, and suggest that pericytes may be an important source of CAFs.

Tepoxalin a dual 5-LOX-COX inhibitor and erlotinib an EGFR inhibitor halts progression of gastric cancer in tumor xenograft mice.

GC is associated with over expression of epidermal growth factor receptor (EGRF), Cyclooxygenase-2 (COX-2) and 5-Lipoxygenase (5-LOX). We postulated that targeting these pathways will result in better treatment efficacy than using a single agent with higher dose which may cause toxicity and resistance. We evaluated Tepoxalin (TPX) a dual 5-LOX-COX inhibitor and Erlotinib (ERB) an EGFR inhibitor alone and combination in MGC-803 injected tumor xenografts mice. Female nude mice were selected and injected subcutaneously with MGC-803 GC cells and were grouped after the tumor model was formed. The treatment of TPX, ERB and their combination was given for 21 days. After treatment protocol proliferating index was measured, expression of apoptosis related proteins, 5-LOX, COX-2, EGFR, vascular endothelial growth factor-C (VEGF-C) and density of lymphatic vessel density was evaluated in tumor tissues. TUNEL assay was done for apoptosis. The outcomes of study revealed that TPX and ERB alone inhibited the growth of tumor but their combination showed a synergistic antitumor activity. TPX and ERB alone resulted in apoptosis and antiproliferative effect, whereas their combination showed highly significant results (P<0.01). TPX alone and its combination with ERB suppressed 5-LOX, COX-2, EGFR and VEGF-C and caused inhibition of lymphangiogenesis, however ERB alone was unable to affect expression of VEGF-C and lymphangiogenesis. The results confirmed combination of TPX and ERB produced a synergistic anticancer and antitumor activity, possibly by promoting apoptosis and antiproliferative effect on tumor cells via suppressing expression of COX-2, 5-LOX, EGFR and VEGF-C.

The Long Noncoding RNA HOTAIR Promotes Colorectal Cancer Progression by Sponging miR-197.

The long noncoding RNA HOX transcript antisense RNA (HOTAIR) has been found to be overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well known, evidence suggests that microRNA-197 (miR-197) might be involved in this event. In the present study, the significance of HOTAIR and miR-197 in the progression of colorectal cancer was detected in vitro and in vivo. We found that HOTAIR expression was significantly increased in colorectal cancer cells and tissues. In contrast, the expression of miR-197 was obviously decreased. We further demonstrated that HOTAIR knockdown promoted apoptosis and inhibited cell proliferation, migration, and invasion in vitro and in vivo. Moreover, HOTAIR modulated the progression of colorectal cancer by competitively binding miR-197. Taken together, our study has identified a novel pathway through which HOTAIR exerts its oncogenic role and provided a molecular basis for potential applications of HOTAIR in the prognosis and treatment of colorectal cancer.

BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1.

BACKGROUND AND OBJECTIVE: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. METHODS: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. RESULTS: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3'UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. CONCLUSION: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis.