Survival-associated alternative splicing events interact with the immune microenvironment in stomach adenocarcinoma.

BACKGROUND: Alternative splicing (AS) increases the diversity of mRNA during transcription; it might play a role in alteration of the immune microenvironment, which could influence the development of immunotherapeutic strategies against cancer. AIM: To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma (STAD) from the database. The overall survival data associated with AS events were used to construct a signature prognostic model for STAD. METHODS: Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model. In STAD, 2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions. Furthermore, the network of splicing factors and overall-survival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD. RESULTS: An eleven-AS-signature prognostic model (CD44|14986|ES, PPHLN1|21214|AT, RASSF4|11351|ES, KIAA1147|82046|AP, PPP2R5D|76200|ES, LOH12CR1|20507|ES, CDKN3|27569|AP, UBA52|48486|AD, CADPS|65499|AT, SRSF7| 53276|RI, and WEE1|14328|AP) was constructed and significantly related to STAD overall survival, immune cells, and cancer-related pathways. The differentially expressed immune-related genes between the high- and low-risk score groups were significantly enriched in cancer-related pathways. CONCLUSION: This study provided an AS-related prognostic model, potential mechanisms for AS, and alterations in the immune microenvironment (immune cells, genes, and pathways) for future research in STAD.

miR­205­3p promotes lung cancer progression by targeting APBB2.

Non­small cell lung cancer (NSCLC), a leading cause of cancer­associated mortality, has resulted in low survival rates and a high mortality worldwide. Accumulating evidence has suggested that microRNAs (miRs) play critical roles in the regulation of cancer progression and the present study aimed to explore the underlying mechanism of miR­205 in NSCLC. Reverse transcription­quantitative PCR was performed, which determined that miR­205 expression was upregulated in NSCLC, and the present study detected the upregulation of miR­205­3p in a number of NSCLC cell lines and NSCLC tissues. In addition, the mediation of amyloid ß precursor protein­binding family B member 2 (APBB2) by miR­205­3p was demonstrated. Moreover, miR­205­3p was predicted to directly target the 3'untranslated region of APBB2, which was confirmed using a dual­luciferase reporter assay. It was found that lentivirus mediated­APBB2 knockdown could promote cellular viability and suppress apoptosis in NSCLC cells, as determined via MTT, TUNEL and flow cytometry assays. Thus, the current findings highlighted the potential promotive impact of miR­205­3p on NSCLC processes and may provide theoretical evidence for miR­205­3p as a potential clinical gene therapy target.

Long non-coding RNA LINC00887 promotes progression of lung carcinoma by targeting the microRNA-206/NRP1 axis.

Long non-coding RNAs (lncRNAs) have been reported to participate in multiple biological processes, including tumorigenesis. In the current study, the function of a novel lncRNA LINC00887 was investigated in lung carcinoma. For this purpose, LINC00887 expression was assessed by reverse-transcription quantitative PCR. Cell viability was determined by the CCK-8 and EdU assays. Cell invasion, migration were assessed by the transwell and wound healing assays, respectively. A dual luciferase assay was used for analysis of the interaction between LINC00887 and miR-206, as well as the relationship of miR-206 with NRP1. A tumor xenograft study was performed to investigate the LINC00887-miR-206-NRP1 axis in vivo. The expression levels of LINC00887 were upregulated in lung carcinoma tissues and cells compared with adjacent tissues or normal cells (BEAS-2B). Knockdown LINC00887 significantly inhibited the proliferation, migration and invasion of lung carcinoma A549 and NCI-H460 cells. Furthermore, LINC00887 was identified as a competing endogenous RNA and to directly interact with miR-206. Mechanistically, miR-206 was demonstrated to regulate neuropilin-1 (NRP1) expression by targeting the NRP1 3'-untranslated region. The results of the present study suggested that the LINC00887-miR-206-NRP1 axis served a critical role in regulating lung carcinoma cell proliferation, migration and invasion. In addition, xenograft tumor model experiments revealed that silencing LINC00887 suppressed lung carcinoma tumor growth of in vivo. In summary, our results suggest that LINC00887 may serve an oncogenic role in lung carcinoma by targeting the miR-206/NRP1 axis, providing a potential therapeutic target for patients with lung carcinoma.

STEAP1 facilitates metastasis and epithelial-mesenchymal transition of lung adenocarcinoma via the JAK2/STAT3 signaling pathway.

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified gene target from prostate cancer, breast cancer, and gastric cancer. However, functions of STEAP1 in lung adenocarcinoma (LUAD) are still unknown. In the present study, we explored the molecular and cellular mechanisms of STEAP1 in LUAD. Western blot and Q-PCR were conducted to detect the protein and mRNA expressions respectively. The cell proliferation was tested by CCK8 assay. The effects of STEAP1 on the metastasis and epithelial-mesenchymal transition (EMT) of LUAD were evaluated by EdU assay, wound healing assay, and transwell migratory assay. H1650, H358, HCC827, H1299, H23, A549, H1693 were selected as human LUAD cell lines in the study. Results have shown that STEAP1 expression was up-regulated in LUAD cells compared with normal lung epithelial cells. Knockdowning of STEAP1 suppressed the proliferation, migration, and invasion of LUAD epithelial cells. Importantly, after comparing the proliferation, migration, and invasion of LUAD to the corresponding control groups treated in STAT3 inhibitor ADZ1480, we found that STEAP1 regulates EMT via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, STEAP1 can serve as a therapeutic target, and it may have important clinical implications for LUAD treatment.

lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway.

HOTAIR, a well-known long noncoding RNAs (lncRNA), has been recognized to contribute to the tumor metastasis in several tumors. But its role in gastric cancer remains elusive. Here, we reported an increase in HOTAIR promoted proliferation and metastasis of gastric cancer cell lines. The HOTAIR and miR-126 level was determined in 15 paired primary gastric cancer tissues and their adjacent noncancerous gastric tissues. Over-expression or downregulation HOTAIR was conducted in AGS or BGC-823 cells to investigate the impact of HOTAIR in proliferation and metastasis. Then dual luciferase reporter assay was utilized to study the interaction between CXCR4 and miR-126. Cells transfected with shHOTAIR or miR-126 mimic were subjected to western blot to investigate the role of SDF-1/CXCR4 signaling in HOTAIR mediated proliferation and metastasis. HOTAIR was highly expressed in gastric cancer tissues and several gastric cancer cell lines. Overexpressed HOTAIR facilitated proliferation and metastasis in vitro while HOTAIR knockdown inhibit proliferation and metastasis. A negative correlation was observed between miR-126 and HOTAIR. And, we also confirmed the decrease in miR-126 in clinic specimen. Furthermore, HOTAIR and miR-126 negatively regulated each other and then increase or decrease CXCR4 expression and downstream pathway, respectively. CXCR4 was confirmed as a direct target of miR-126. Our study demonstrated that high HOTAIR expression promote proliferation and metastasis in gastric cancer via miR-126/CXCR4 axis and downstream signaling pathways.

Prognostic significance of pretreatment serum carcinoembryonic antigen levels in gastric cancer with pathological lymph node-negative: A large sample single-center retrospective study.

AIM: To assess whether elevated serum carcinoembryonic antigen (CEA) is in the inferior prognosis for pathological lymph node-negative (pN0) gastric cancer (GC) patients who underwent D2 gastrectomy. METHODS: About 469 pN0 GC patients, who received D2 radical gastrectomy were retrospectively analyzed. The X-tile plots cut-off point for CEA were 30.02 ng/mL using minimum P-value from log-rank χ2 statistics, and pN0 GC patients were assigned to two groups: those more than 30.02 ng/mL (n = 48; CEA-high group) and those less than 30.02 ng/mL (n = 421; CEA-low group). Clinicopathologic characteristics were compared using Pearson's χ2 or Fisher's exact tests, and survival curves were so manufactured using the Kaplan-Meier method. Univariate and multivariate analysis were carried out using the logistic regression method. RESULTS: The percentage of vessel carcinoma embolus (31.35% vs 17.1%) and advanced GC (T2-4b) (81.25% vs 65.32%) were higher in CEA-high group than CEA-low group. The CEA-positive patients had a significantly poorer prognosis than the CEA-nagetive patients in terms of overall survival (57.74% vs 90.69%, P < 0.05), and no different was found between subgroup of T category, differentiation, nerve invasion, and vessel carcinoma embolus (all P > 0.05). Multivariate survival analysis showed that CEA (OR = 4.924), and T category (OR = 2.214) were significant prognostic factors for stage pN0 GC (all P < 0.05). Besides, only T category (OR = 1.962) was an independent hazard factor in the CEA-high group (P < 0.05). CONCLUSION: Those pretreatment serum CEA levels over 30.02 ng/mL on behalf of worse characteristics and unfavourable tumor behavior, and a poor prognosis for a nearly doubled risk of mortality in GC patients.

Factors influencing the quality of life of 104 children with phenylketonuria in Anhui Province, China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the factors influencing the quality of life (QOL) of children with phenylketonuria (PKU) in Anhui Province, China.</p><p><b>METHODS</b>A total of 104 PKU children who were diagnosed and treated in three major maternal and child health hospitals in Anhui Province were enrolled as study subjects. The PedsQL™ 4.0 Generic Core Scales were used to evaluate the quality of life of these children. The multivariate logistic regression analysis was used to evaluate the factors influencing the QOL.</p><p><b>RESULTS</b>The 104 PKU children had significantly lower overall QOL score and scores on the subscales of physiological functioning, emotional functioning, and social functioning than the general school-age children (P<0.01). They also had a significantly lower score on the physiological domain consisting of emotional functioning, social functioning, and role functioning than the general school-age children (P<0.01). The multivariate logistic regression analysis showed that an older age (≥4 years) of PKU children was the risk factor for poor QOL (OR=8.569, P<0.01), and guardians' engagement at enterprises or institutions was the protective factor for QOL (OR=0.206, P<0.05).</p><p><b>CONCLUSIONS</b>PKU children have a low level of QOL, and age and guardians' occupation are factors influencing the QOL.</p>