Case report: Coexistence of sigmoid tumor with unusual pathological features and multiple colorectal neuroendocrine tumors with lymph node metastases.

The coexistence of adenocarcinoma and neuroendocrine neoplasm (NEN) in the same tumor is rare. What is rarer is that the neuroendocrine component is a well-differentiated neuroendocrine tumor (NET) Grade (G) 1. Most colorectal NETs are single, but multiple neuroendocrine tumors (M-NETs) are rare. Well-differentiated NETs rarely metastasize. Here, we present a unique case of a synchronous sigmoid tumor and multiple colorectal NETs with lymph node metastases. The sigmoid tumor consisted of adenocarcinoma and NET G1. The metastatic component was NET G1. A 64-year-old man underwent a colonoscopy for persistent changes in bowel habits and positive fecal occult blood for 1 year. An ulcerative lesion, which was diagnosed as colon cancer, was seen in the sigmoid colon. In addition, scattered lesions could be seen in the colon and rectum. Surgical resection was performed. Pathological findings suggested that the ulcerative lesion was composed of 80% adenocarcinoma and 20% neuroendocrine component (NET G1), while the remaining lesions were consistent with NET G1. At the same time, 11 lymph nodes around the resected intestinal segment were invaded by NET G1. The prognosis of the patient was good. After 13 months of follow-up, no recurrence and no metastasis were found. We hope to provide a reference and improve our understanding of the clinicopathological features and biological behavior of these unique tumors. We also aim to emphasize the importance of radical surgery and individualized treatment.

Role of N6­methyladenosine in the pathogenesis, diagnosis and treatment of pancreatic cancer (Review).

Pancreatic cancer (PC) ranks as the seventh leading cause of cancer­associated mortality, and is predicted to become the third leading cause of cancer­associated mortality by the year 2025. Although advanced modalities of diagnosis and treatment have been continuously emerging, the mortality rate (466,003) approximated to that of the morbidity rate (495,773) in 2020. N6­methyladenosine (m6A) has been shown to be methylated on the sixth N atom of adenine in RNA, which occurs co­transcriptionally and serves to regulate gene expression post­transcriptionally. The discovery of m6A has heralded a new era in the scientific investigation of PC. In the present review article, the classical conception of m6A and emerging hypotheses regarding its role are summarized, and the function of m6A in carcinogenesis and progression of PC is then discussed, followed by the potential roles of m6A in the diagnosis of PC and in therapeutic applications. However, this new era is only at the initial stages, and the extent to which m6A influences PC is still poorly understood. In view of this, the present review article also summarizes the developments at the frontier of the interaction between m6A and PC, and discusses strategies through which m6A may provide a promising avenue for anticancer therapy.

N6-methyladenosine Modification of Noncoding RNAs: Mechanisms and Clinical Applications in Cancer.

N6-methyladenosine (m6A) modification remains the most pivotal epigenetic modification on RNA. As we know, m6A not only affects physiological processes but is also involved in carcinoma. Noncoding RNAs play an indispensable role in the occurrence and development of carcinoma. However, a large amount of research is focused on mRNA currently. Insufficient research has been done on the relationship between noncoding RNA (ncRNA) methylation and cancer. Therefore, this review aims to introduce the theoretical knowledge of m6A modification in noncoding RNA, discuss its function in tumorigenesis and progression, and ultimately summarize its potential clinical applications.

Multiple rectal neuroendocrine tumors: An analysis of 15 cases and literature review.

Multiple neuroendocrine tumors (M-NETs) are rare in the rectum and there is no consensus on their characteristics and treatments. Here, we report 15 cases of rectal M-NETs and review the previous literature. We discuss the clinical characteristics, endoscopic features and pathological features of rectal M-NETs, aiming to analyze the treatments and follow-up strategies in combination with these characteristics. We retrospectively reviewed and analyzed the data of 15 patients with rectal M-NETs who were diagnosed and treated at Beijing Friendship Hospital, Capital Medical University. Their clinical data, endoscopic findings, pathological features and treatments were analyzed. Follow-up evaluations and literature review were performed. In all, 14 male (93.3%) and 1 female (6.7%) were recruited. The average age at diagnosis was 55.7 years. The clinical manifestations include asymptomatic in 9 patients (60.0%), defecation habits changes in 2 patients (13.3%), anal distension in 2 patients (13.3%), and abdominal distension in 2 patient (13.3%). The largest tumor diameter ≤10mm was found in 13 patients (86.7%) and >10mm in 2 patients (13.3%). All of the lesions originated from the mucous or submucosa layer. WHO grades were all NET G1. The number of tumors diagnosed by pathology in 13 patients was consistent with that observed by endoscopy, while more lesions were observed by pathology than endoscopy in two patients. Lymph node metastasis occurred in 1 patient (6.7%), and vascular or lymphatic invasion occurred in 9 patients (60.0%). Among the 13 patients with the largest tumor diameter being ≤10mm, lymphovascular invasion occurred in 8 patients (61.5%). And among the 2 patients with the largest tumor diameter of >10mm, lymphovascular invasion occurred in 1 patient (50.0%). 14 patients underwent endoscopic resection and 1 underwent surgical excision. Postoperative follow-up was achieved in 13 patients and no recurrence or metastasis was found. The true number of rectal M-NETs may be more than seen under endoscopy. Rectal M-NETs is associated with a high risk of metastasis; therefore, treatment and surveillance strategies should be more radical than single lesion.

TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment.

As an important component of the immunosuppressive tumor microenvironment (TME), it has been established that mesenchymal stem cells (MSCs) promote the progression of tumor cells. MSCs can directly promote the proliferation, migration, and invasion of tumor cells via cytokines and chemokines, as well as promote tumor progression by regulating the functions of anti-tumor immune and immunosuppressive cells. MSCs-derived extracellular vesicles (MSCs-EVs) contain part of the plasma membrane and signaling factors from MSCs; therefore, they display similar effects on tumors in the immunosuppressive TME. The tumor-promoting role of macrophage migration inhibitory factor (MIF) in the immunosuppressive TME has also been revealed. Interestingly, MIF exerts similar effects to those of MSCs in the immunosuppressive TME. In this review, we summarized the main effects and related mechanisms of tumor-associated MSCs (TA-MSCs), TA-MSCs-EVs, and MIF on tumors, and described their relationships. On this basis, we hypothesized that TA-MSCs-EVs, the MIF axis, and TA-MSCs form a positive feedback loop with tumor cells, influencing the occurrence and development of tumors. The functions of these three factors in the TME may undergo dynamic changes with tumor growth and continuously affect tumor development. This provides a new idea for the targeted treatment of tumors with EVs carrying MIF inhibitors.

Application of engineered extracellular vesicles for targeted tumor therapy.

All cells, including prokaryotes and eukaryotes, could release extracellular vesicles (EVs). EVs contain many cellular components, including RNA, and surface proteins, and are essential for maintaining normal intercellular communication and homeostasis of the internal environment. EVs released from different tissues and cells exhibit excellent properties and functions (e.g., targeting specificity, regulatory ability, physical durability, and immunogenicity), rendering them a potential new option for drug delivery and precision therapy. EVs have been demonstrated to transport antitumor drugs for tumor therapy; additionally, EVs' contents and surface substance can be altered to improve their therapeutic efficacy in the clinic by boosting targeting potential and drug delivery effectiveness. EVs can regulate immune system function by affecting the tumor microenvironment, thereby inhibiting tumor progression. Co-delivery systems for EVs can be utilized to further improve the drug delivery efficiency of EVs, including hydrogels and liposomes. In this review, we discuss the isolation technologies of EVs, as well as engineering approaches to their modification. Moreover, we evaluate the therapeutic potential of EVs in tumors, including engineered extracellular vesicles and EVs' co-delivery systems.

Mesenchymal stem cell-derived exosome: A tumor regulator and carrier for targeted tumor therapy.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that have the ability to differentiate into multiple cell types. Several studies have shown that exosomes secreted by MSCs (MSCs-Exo) play an important role in tumor growth, angiogenesis, invasion, and drug resistance. However, contradictory results have suggested that MSCs-Exo can also suppress tumors through specific mechanisms, such as regulating immune responses and intercellular signaling. Consequently, the relationship between MSCs-Exo and tumors remains controversial. However, it is undeniable that exosomes, as natural vesicles, can be excellent drug carriers and show promise for application in targeted tumor therapy. Here, we review the current knowledge regarding the involvement of MSCs-Exo in tumor progression and their potential as drug delivery systems in targeted therapy. We argue that MSCs-Exo can be used as safe carriers of antitumor drugs.

Characteristics of endoscopic and pathological findings of amebic colitis.

BACKGROUND: The clinical features of amoebic colitis resemble those of inflammatory bowel disease (IBD), and therefore the risk of misdiagnosis is very high. The aim of this study was to analyse the characteristics of the endoscopic and pathological findings of amebic colitis and the lessons from our patients, which were useful for diagnosing the amebic colitis timely and avoiding the serious complication. METHODS: We retrospectively reviewed data of all amebic colitis admitted to Beijing Friendship Hospital from January 2015 to January 2020. Cases were diagnosed by clinical presentation, laboratory examinations, and colonoscopy with biopsy and histological examination, no ELISA stool antigen or PCR tests were used. RESULTS: 16 patients were diagnosed with amebic colitis by the colonoscopy accompanied by biopsy and microscopic examination. At first time, 12 (75%) patients were misdiagnosed as IBD. Cecum was the most common site of amebic colitis (100%), and the caecum and rectum were also involved in many lesions (68.75%). Multiple lesions of erosion and/or ulcer were recognized in all patients (100%).The endoscopic findings included multiple irregular shaped ulcers and erosions with surrounding erythema, and the ulcers and erosions were covered by the white or yellow exudates. The intervening mucosae between the ulcers or erosions were normal. The features of rectums can be divided to 2 types: in 6 patients (54.5%), the irregular ulcer or erosions covered with white or yellow exudates were observed in rectum and cecum, and the bloody exudates in rectum were more severe than those in cecum; in other 5 patients (45.5%), rectal lesions were much less severe than those in cecum, the small superficial erosion or reddened mucosa were observed in the rectal ampulla. All patients were diagnosed as detection of amebic trophozoites from HE-stained biopsy specimens. The number of trophozoites ranged from 1/HPF to > 50/HPF. Among 16 cases, mild architectural alteration of colon crypt were observed in 10 cases (62.5%), and serious architectural alteration of colon crypt was found which had crypt branch in 1 case (16.7%). Cryptitis was observed in 12 cases (75%) and its severity was mild or moderate. No crypts abscess was observed in all cases. CONCLUSIONS: The colonoscopy with histological examination are very important to diagnose the amebic colitis. Detect the amoebic trophozoites in the exudates by histological examination is the vital. Sometimes a negative biopsy does not rule out amebiasis, repeated biopsies may be needed to make the diagnosis.

5-HTP decreases goat mammary epithelial cells apoptosis through MAPK/ERK/Bcl-3 pathway.

Serotonin (5-HT) is a monoamine and it could regulate cell growth by its receptors working on signaling pathways. 5-HTP is the precursor of 5-HT that help 5-HT synthesis. B cell leukemia/lymphoma 3 (Bcl-3) involved in cell death and proliferation through mitogen activated protein kinase (MAPK) pathway. However, there is little information about the effects of MAPK/Bcl-3 on apoptosis of goat mammary gland epithelial cells (GMECs). The aim of this study is to explore the interaction among 5-HTP, MAPK and Bcl-3 in GMEC apoptosis. In this study, 5-HTP treatment decreased cell apoptosis and promoted phosphorylation of ERK1/2 in GMEC. We also found that the activation and inhibition of ERK1/2 could affect GMEC apoptosis. The Annexin V-FITC/PI staining and western blotting results suggested that 5-HTP decreased GMEC apoptosis through ERK1/2 signaling pathway. And the results of RT-qPCR and western blotting demonstrated that both 5-HTP and ERK1/2 positively regulated Bcl-3 expression. Sum up all the results, we could draw the conclusion that 5-HTP decreased GMEC apoptosis through MAPK/ERK/Bcl-3 pathway.

HDAC3-dependent transcriptional repression of FOXA2 regulates FTO/m6A/MYC signaling to contribute to the development of gastric cancer.

As one of the deadliest malignancies, gastric cancer (GC) is often accompanied by a low 5-year survival following initial diagnosis, which accounts for a substantial proportion of cancer-related deaths each year worldwide. Altered epigenetic modifications of cancer oncogenes and tumor suppressor genes emerge as novel mechanisms have been implicated the pathogenesis of GC. In the current study, we aim to elucidate whether histone deacetylase 3 (HDAC3) exerts oncogenic role in GC, and investigate the possible mechanism. Initially, we collected 64 paired cancerous and noncancerous tissues surgically resected from GC patients. Positive expression of HDAC3, FTO, and MYC in the tissues was measured using Immunohistochemistry. Meanwhile, GC cell line BGC-823/AGS was selected and treated with lentivirus vectors for alteration of HDAC3, FTO, or FOXA2 expressions, followed by detection on mRNA and protein levels of HDAC3, FOXA2, FTO, and MYC using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The results demonstrated that the expressions of HDAC3, FTO and MYC were upregulated, while FOXA2 expression was downregulated in GC tissues and cells. After that, the cell viability, migration, and invasion of GC cells were assessed by CCK-8 and Transwell assays, revealing that HDAC3 accelerated GC cell viability, migration and invasion by degrading FOXA2. Subsequently, the binding relationship among HDAC3, FOXA2, FTO, and MYC was assessed by assays of immunoprecipitation, dual-luciferase reporter gene, and chromatin immunoprecipitation assay. Methylation of m6A mRNA in GC cells was detected via gene-specific m6A qPCR and dot-blot assays. The transcription factor FOXA2 was found to bind to the FTO gene promoter and decreased its expression, while FTO stabilized MYC mRNA by reducing m6A methylation of MYC in GC cells. In addition, HDAC3 was observed to maintain the FTO/m6A/MYC signaling and regulated GC progression, which was also supported by in vivo animal study data of GC cell tumorigenesis in nude mice. These key observations uncover the tumor-initiating activities of HDAC3 in GC through its regulation on FOXA2-mediated FTO/m6A/MYC axis, highlighting the potential of therapeutically targeting epigenetic modifications to combat GC.

Differences between intentional and accidental ingestion of foreign body in China.

BACKGROUNDS: Previous reports of foreign-body ingestion focused primarily on accidental ingestion and very few studies focused on intentional ingestion of foreign body (FB) in China. Our study aimed to compare the prevalence of different age, gender, types, locations and management of FB ingested between intentional ingestion and accidental ingestion of FB in Northern China. METHODS: A retrospective case series studied all patients with suspected FB ingestion in Digestive Endoscopy Center of Beijing Friendship Hospital, between January 2011 and January 2019. The patients were divided into 2 groups. Group A included the patients who intentionally ingested FBs, and Group B included the patients who accidentally ingested FBs. Patients' database (demographics, past medical history, characteristics of FB, endoscopic findings and treatments) were reviewed. Statistical analyses were conducted using SPSS software. RESULTS: Group A consisted of 77 prisoners, 2 suspects and 11 psychologically disabled persons. Group B consisted of 1020 patients with no prisoners, suspects or psychologically disabled persons. In Group A, there were no food-related foreign bodies, and the majority of FBs were metallic objects (54.44%). However in Group B, food-related FBs were the most common (91.37%). In Group A, 58 cases (64.44%) were located in the stomach, while in Group B, 893 cases (87.55%) were located in the esophagus (P < 0.05). 1096 patients successfully underwent endoscopic removal and 14 failed, including 9 cases in Group A and 5 cases in Group B. The duration of FBs impaction was longer in Group A than that in Group B (P < 0.05). CONCLUSIONS: In our study, the patients who intentionally ingested FB were mainly prisoners, FBs were mostly sharp metallic objects, the duration of FBs impaction was longer, and the rate of successful endoscopic treatment was lower than that of the general population. Attention should be focused on these patients.

5-Hydroxy-l-tryptophan Promotes the Milk Calcium Level via the miR-99a-3p/ATP2B1 Axis in Goat Mammary Epithelial Cells.

5-Hydroxy-l-tryptophan (5-HTP) is the primary product that converts l-tryptophan into 5-hydroxytryptamine by a rate-limiting enzyme. Our previous study found that 5-HTP could promote the intracellular calcium level in goat mammary epithelial cells (GMECs). Herein, first, dairy goats were injected with 5-HTP or saline daily from 7 days before delivery, and the calcium level in colostrum of 5-HTP-injected goats was significantly higher than that of saline-injected goats. Moreover, miR-99a-3p expression was significantly increased after 5-HTP treatment from transcriptome sequencing analysis and quantitative real-time polymerase chain reaction. In addition, it was found that ATP2B1 is one of the target genes of miR-99a-3p predicted by bioinformatic methods, which plays a crucial role in the maintenance of intracellular calcium homeostasis of mammary epithelial cells. Next, we confirmed that miR-99a-3p could increase the intracellular calcium level via decreasing ATP2B1 in GMECs. Taken together, we draw the conclusion that 5-HTP promotes the calcium level in colostrum possibly by increasing intracellular calcium of mammary epithelial cells induced by the miR-99a-3p/ATP2B1 axis.

New ferrocene-triazole derivatives for multisignaling detection of Cu2+ in aqueous medium and their antibacterial activity.

Ferrocene-based naphthalene or quinoline receptors 1-4 linked by triazole were designed and synthesized. Their recognition properties of metal cations have been investigated systematically in aqueous environment. Upon addition 1 equiv. of Cu2+ ion, receptors 1 (C23H19FeN3O) and 2 (C22H18FeN4O) showed fluorescent turn-off, enhanced absorption and color variations. At the same time, receptor 1 also caused the perturbation of redox potential after addition 1 equiv. of Cu2+ ion. Therefore, receptors 1 and 2 behaved as naked-eye chemosensors and fluorescent probes for Cu2+ without interference by other ions and with low detection limit. In addition, receptor 1 could also be considered electrochemical sensor for Cu2+ having excellent sensitivity and selectivity. However, increasing the molecules flexibility resulted in the lower selectivity of ion recognition in the case of receptors 3 (C24H21FeN3O) and 4 (C23H20FeN4O). Furthermore, this series of compounds were nontoxicity and receptor 1 exhibited certain antibacterial activity.

Prevalence of CYP17A1 gene mutations in 17α-hydroxylase deficiency in the Chinese Han population.

BACKGROUND: 17α-hydroxylase deficiency is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 gene. The major clinical presentation includes hypertension, hypokalemia, male pseudohermaphroditism and female gonadal dysplasia. Hundreds of pathogenic variants have been reported in this disorder, and some common mutations were found to be race-specific. CASE PRESENTATION: In this study, we reported 5 Chinese girls with 17α-hydroxylase deficiency from Henan Province. The patients all came to the hospital for hypertension, and they also presented with sexual infantilism. The average age of the patients was 14 years old, ranging from 12 to 17 years old. They all had reduced blood cortisol, estradiol (E2), and testosterone (TESTO) and increased adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). They all had the appearance of females; however, three of the chromosome karyotypes were 46XX, and two were 46XY. CONCLUSIONS: All of the patients carried a mutation on the 329 amino acid of CYP17A1 exon 6. By summarizing the currently known pathogenic mutations of 17α-hydroxylase deficiency, we demonstrated the prevalence of these gene mutations in Chinese Han and non-Chinese populations.

EBV-associated lymphoproliferative disorder involving the gastrointestinal tract which mimic IBD in immunocompetent patients: case reports and literature review.

INTRODUCTION: Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (LPD) with digestive tract involvement in immunocompetent patients is rather rare. Since the symptoms of EBV-associated LPD involving the gastrointestinal tract in immunocompetent patients are similar to those of inflammatory bowel disease (IBD), most patients are initially misdiagnosed. CASE PRESENTATION: In this paper, we present two cases of EBV-associated T cell LPD involving the colon in immunocompetent patients and review the relevant literature. CONCLUSION: EBV serological testing may help in detecting this disease, and our findings suggest that histopathological evidence of EBV, such as the Epstein-Barr encoding region, is very important to establish the diagnosis.

Complete excision of esophageal bronchogenic cyst by endoscopic submucosal tunnel dissection: a case presentation.

BACKGROUND: Intramural esophageal bronchogenic cyst is very rare. Surgical removal of the cysts is advised even the patients are asymptomatic, since the cyst can lead to complications, and there is a risk of malignant transformation. Thoracotomy or thoracoscopy is the most commonly used approach for complete excision of the cysts. To our knowledge, this is the first report to excise intramural esophageal bronchogenic cyst completely by endoscopic submucosal tunnel dissection (ESTD). CASE PRESENTATION: A 40-year-old male was referred to our hospital due to the detection of a submucosal tumor at the distal esophagus. The tumor was found during gastroendoscopy in a general health check-up. The patient had no symptoms. A benign esophageal tumor was confirmed by endoscopic ultrasonography (EUS) and computed tomography (CT). On the basis of these results, ESTD was performed. During the procedure, a cystic mass was observed between the mucosa and the muscular layers of the esophagus, and a hybrid knife was used for dissection. Histopathological examination showed the cyst wall was lined by pseudostratified ciliated columnar epithelium, consistent with a bronchogenic cyst. The esophagography using meglumine diatrizoate showed no leakage on the seventh day after ESTD. The patient remained asymptomatic and had a regular diet during the follow-up period. DISCUSSION AND CONCLUSIONS: We successfully utilized ESTD for complete removal of esophageal bronchogenic cysts originating from the muscularis propria. The approach appeared safe, providing a minimally invasive treatment option for patients.

Silencing of Long Non-coding RNA SMAD5-AS1 Reverses Epithelial Mesenchymal Transition in Nasopharyngeal Carcinoma via microRNA-195-Dependent Inhibition of SMAD5.

Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years as a key regulator of diverse biological processes, but the knowledge of the mechanisms by which they act is still very limited. Differentially expressed lncRNA SMAD5 antisense RNA 1 (SMAD5-AS1) in nasopharyngeal carcinoma (NPC) and normal samples shown by in silico analyses were selected as the main subject, and then microRNA-195 (miR-195) was suggested to bind to SMAD5-AS1 and SMAD5. Therefore, the purpose of the present study was to investigate the effects of SMAD5-AS1/miR-195/SMAD5 on epithelial-mesenchymal transition (EMT) in NPC cells. High expression of SMAD5-AS1 and SMAD5 but low miR-195 expression was determined in NPC tissues and NPC cell lines by RT-qPCR and western blot analysis. SMAD5-AS1 could upregulate SMAD5 expression by competitively binding to miR-195 in NPC cells. Loss- and gain-of-function investigations were subsequently conducted in NPC cells (CNE-2 and CNE-1) to explore the role of SMAD5-AS, miR-195 and SMAD5 in NPC progression by assessing cellular biological functions and tumorigenic ability in vivo as well as determining the expression of EMT markers. Downregulation of SMAD5-AS1 or SMAD5 or overexpression of miR-195 led to inhibited NPC cell proliferation, invasion and migration and reversed EMT, enhanced apoptosis in vitro as well as restrained tumor growth in vivo. In conclusion, our findings indicate that silencing of lncRNA SMAD5-AS1 induces the downregulation of SMAD5 by miR-195, eventually repressing EMT in NPC. Hence, SMAD5-AS1 may represent a potential therapeutic target for NPC intervention.

TCF21 inhibits proliferation and chemoresistance through the AKT pathway in human gastric cancer.

In a previous study, we showed that transcription factor 21 (TCF21) is methylated and downregulated in human gastric cancer samples and serves as an independent prognostic factor. However, its biological role and potential mechanism in gastric cancer cells remain unexplored. In the current study, we examined TCF21 expression in 6 gastric cancer cell lines. The BGC-823 and SGC-7901 cell lines were selected for small interfering RNA and plasmid transfection, respectively. The results of the Cell Counting Kit-8 assay demonstrated that TCF21 inhibited gastric cancer cell proliferation. Cell cycle analysis suggested that TCF21 inhibited cell cycle progression in gastric cancer cells. The Matrigel invasion assay demonstrated that TCF21 negatively regulated invasion. The cell adhesion assay showed that TCF21 increased cell adhesion. Gastric cancer cells were treated with cisplatin to explore the role of TCF21 in chemoresistance. Cell Counting Kit-8 assay and AnnexinV/propidium iodide analyses showed that TCF21 overexpression sensitized SGC-7901 cells to cisplatin, whereas its depletion reduced sensitivity in BGC-823 cells. JC-1 staining was performed to measure the effect of TCF21 on mitochondrial potential. TCF21 downregulated mitochondrial membrane potential after treatment with cisplatin. Western blot analysis showed that TCF21 overexpression negatively regulated Bcl-xL, phosphorylated extracellular signal regulated kinase, and phosphorylated AKT expression and induced caspase 3 cleavage. LY294002, an AKT inhibitor, blocked the effect of TCF21 on Bcl-xL, caspase 3 and CDDP-induced apoptosis. Nude mice experiments demonstrated that TCF21 inhibited gastric cancer growth in vivo. In conclusion, our results suggest that TCF21 inhibits gastric cancer growth and chemoresistance possibly through the AKT signaling pathway.

Noncoding RNA activated by DNA damage (NORAD): Biologic function and mechanisms in human cancers.

Noncoding RNA activated by DNA damage (NORAD) is a newly identified long non-coding RNA (lncRNA) comprising one exon located on Chr20q11.23. NORAD is unique among lncRNAs because it is highly conserved, abundantly expressed, upregulated upon DNA damage, and maintains chromosomal stability in human cells. NORAD is dysregulated in different types of cancers and has been implicated in several processes correlated with carcinogenesis, such as cell proliferation, invasion, metastasis, and apoptosis. The mechanisms underlying the effects of NORAD are complex and involve multiple factors and signaling pathways. The biologic function and mechanisms of NORAD in human cancers are systematically reviewed here to provide new directions for future research.