Diagnostic value of long noncoding RNA SNHG15 in gastric cancer: in vitro and in silico studies.

LncRNA SNHG15 has been recognized as the main factor in the progression of various cancer types. However, the underlying mechanisms are not well clarified. This research aimed to explore the diagnostic potential of SNHG15 in gastric cancer (GC) patients and also the effects of SNHG15-miRNA-mRNA network in GC pathobiology. The expression level of SNHG15 in GC tissues and adjacent normal tissues (ANTs) was evaluated by qRT-PCR and also considered in relation to clinicopathologic factors. The ROC curve was explored to consider the specificity and sensitivity of SNHG15. Gene ontology functional annotation and KEGG pathway analysis were performed in order to predict the effects of SNHG15-miRNA-mRNA network in GC pathobiology. SNHG15 was overexpressed in GC tissues compared to ANTs (fold change= 3.87 and P-value = 0.0022). The SNHG15 expression level was not significantly associated with clinicopathologic factors. ROC curve indicated the specificity of 63.51 and sensitivity of 79.73 and the AUC of 0.744 (P-value < 0.0001). Further gene network analysis revealed that SNHG15 interacts with has-miR-613, has-miR-542-3p, and has-miR-1236-3p, and may be involved in the GC pathobiology by affecting the EGFR tyrosine kinase inhibitor resistance, HIF-1 signaling pathway, and VEGF signaling pathway. It can be concluded that SNHG15 may be a diagnostic factor in GC and may contribute in a variety of cancer-related signaling pathways.

Long noncoding RNA polymorphisms in gynecological cancers.

Gynecological malignancies are one of the main causes of cancer-induced mortality. Despite remarkable recent therapeutic advances, current therapeutic options are not sufficient. Regarding the effect of long noncoding RNAs (lncRNAs) on cell differentiation, proliferation and apoptosis, variations in their expression cause different anomalies, such as tumorigenesis. SNPs influence lncRNA function and expression. LncRNA polymorphisms can predict cancer risk and are effective for early diagnosis and customized therapy. In this literature review, we comprehensively investigate the effect of lncRNA polymorphisms on gynecological cancers. LncRNA-related variants are proposed to evaluate cancer incidence, early detection and management of personalized therapy. Nonetheless, more studies are required to validate the consistency of current findings in numerous samples and across various ethnic groups.

Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?

Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual impairment in the elderly. The current management of nAMD is limited and involves regular intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF). However, the effectiveness of these treatments is limited by overlapping and compensatory pathways leading to unresponsiveness to anti-VEGF treatments in a significant portion of nAMD patients. Therefore, a system view of pathways involved in pathophysiology of nAMD will have significant clinical value. The aim of this study was to identify proteins, miRNAs, long non-coding RNAs (lncRNAs), various metabolites, and single-nucleotide polymorphisms (SNPs) with a significant role in the pathogenesis of nAMD. To accomplish this goal, we conducted a multi-layer network analysis, which identified 30 key genes, six miRNAs, and four lncRNAs. We also found three key metabolites that are common with AMD, Alzheimer's disease (AD) and schizophrenia. Moreover, we identified nine key SNPs and their related genes that are common among AMD, AD, schizophrenia, multiple sclerosis (MS), and Parkinson's disease (PD). Thus, our findings suggest that there exists a connection between nAMD and the aforementioned neurodegenerative disorders. In addition, our study also demonstrates the effectiveness of using artificial intelligence, specifically the LSTM network, a fuzzy logic model, and genetic algorithms, to identify important metabolites in complex metabolic pathways to open new avenues for the design and/or repurposing of drugs for nAMD treatment.

Risk of Gastric Cancer is Highly Dependent on Type of First-Degree Family Member Affected by Cancer: Lessons from a High-Risk Population in Iran.

Background: Family history of gastric cancer (GC) in first-degree relatives may increase the risk of GC. This study aimed to assess how family history of GC in first-degree relatives really affects the risk of GC in an extremely high-risk population. Methods: A large population-based case-control study was carried out on 1222 incident GC cases and 1235 controls in Ardabil Province-a high-risk area in North-West Iran-to assess the associations of GC family history in first-degree relatives with the risk of GC (2003-2017). Results: GC family history did not significantly associate with the risk of GC overall (ORadj=1.09, 95% CI: 0.80-1.47, P=0.589). It found no significant association of GC family history in a parent, and in a father, mother, and sister separately, with the risk of GC. However, GC risk was significantly associated with a history of GC in a sibling (ORadj=1.61, 95% CI: 1.11-2.35, P=0.013), especially brother (ORadj=2.24, 95% CI: 1.41-3.64, P=0.0008). The risk was greatly increased in subjects with two or more affected brothers (ORadj =5.56, 95% CI: 2.33-14.20, P=0.0002). Conclusion: We did not find a familial tendency to cardia GC and non-cardia GC as well as histopathologic features. Determining the type of first-degree relationships with GC may, therefore, be more important than assessing family history alone for predicting the risk of GC in this high-risk area.

LncRNA polymorphisms and lung cancer risk.

Lung cancer (LC) imposes a significant burden, and is associated with high mortality and morbidity among malignant tumors. Aberrant expression of particular lncRNAs is closely linked to LC. LncRNA polymorphisms cause abnormal expression levels and/or structural dysfunction. They can affect the progression of cancer, survival, response to chemotherapy and recurrence rates in cancer patients. The present article provides a comprehensive overview of the effect of lncRNA genetic polymorphisms on LC. It is proposed that lncRNA-related variants can be used to predict cancer risk and therapeutic outcomes. More large-scale trials on diverse ethnic groups are required to validate the results, thus personalizing LC therapy based on lncRNA genotypes.

Clinical application of circulating tumor DNA in metastatic cancers.

INTRODUCTION: Advances in genomics have facilitated the application of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in phase II and phase III clinical trials. The various mutations of cfDNA/ctDNA have been correlated with clinical features. Advances in next-generation sequencing (NGS) and digital droplet PCR have paved the way for identifying cfDNA/ctDNA mutations. AREAS COVERED: Herein, the biology of ctDNA and its function in clinical application in metastasis, which may lead to improved clinical management of metastatic cancer patients, are comprehensively reviewed. EXPERT OPINION: Metastatic cancer ctDNA shows the greatest frequency of mutations in TP53, HER-2, KRAS, and EGFR genes (alteration frequency of > 50%). Therefore, identifying key mutations frequently present in metastatic cancers can help identify patients with pre-malignant tumors before cancer progression. Studying ctDNA can help determine the prognosis and select appropriate treatments for affected patients. Nevertheless, the obstacles to detecting and analyzing ctDNA should be addressed before translation into routine practice. Also, more clinical trials should be conducted to study the significance of ctDNA in commonly diagnosed malignancies. Given the recent advances in personalized anti-neoplastic treatments, further studies are needed to detect a panel of ctDNA and patient-specific ctDNA for various cancers.

Long noncoding RNA polymorphisms and hepatocellular carcinoma and pancreatic cancer risk.

Hepatocellular carcinoma (HCC) and pancreatic cancer (PC) are among serious malignancies with no proper biomarker suffering from poor prognosis and late onset. Regulation of long noncoding RNAs (lncRNAs) is disturbed in tumors, making them appropriate diagnostic markers or therapeutic targets in systemic therapies. The expression and function of some significant lncRNAs are under the influence of SNPs, highlighting their key role in carcinogenesis. This review assesses the associations between SNPs in lncRNAs and HCC and PC risk. A panel of cancer-associated SNPs in lncRNA genes could help evaluate the clinical use of lncRNAs, including their role as diagnostic markers and therapeutic targets. Nonetheless, more large-scale surveys on various ethnic groups are required to validate results.

Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations.

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.

Emerging long noncoding RNA polymorphisms as novel predictors of survival in cancer.

Long non coding RNAs (lncRNAs) are involved in the tumor growth, invasion, metastasis, and cancer recurrence. The improper expression of certain lncRNAs is correlated with the prognosis of the cancer patients. LncRNA single nucleotide polymorphisms (SNPs) largely affect the expression, structure, and function of lncRNAs. Therefore, they affect cancer prognosis and susceptibility. In the present review, we tried to collect all published papers on the prognostic ability in cancer considering the correlation of different lncRNAs polymorphism and survival. We explored the association between lncRNA (i.e. MALAT1, ANRIL, GAS5, TP73-AS1, HOTAIR, H19, LncARSR, PVT1, HOTTIP, PRNCR1, PCAT1, CASC8, UCA1, SNHG5, PARP1, Linc00312, and NEAT) polymorphisms with cancer prognosis. The HOTAIR rs920778/rs4759314 and MALAT1 rs664589 polymorphisms play an important role in cancer relevant functions. Other lncRNAs polymorphisms are special for certain kinds of cancer, indicating their function in specific signaling pathways. Accordingly, the individual or combined genotypes of lncRNA polymorphisms are able to predict cancer prognosis. However, most of the samples are Chinese and do not represent the global population. More large-scale trials of different ethnic groups as well as comprehensive health records are therefore needed for more validation of the results.

DNA Banking to Assess Genetic Influences on Schizophrenia.

Background: Schizophrenia is among the most prevalent psychiatric disorders globally, with a lifetime prevalence rate of 0.3% to 0.7%, characterized by the heterogeneous presence of positive, negative, and cognitive symptoms that affect all aspects of mental activity. We aimed to describe the genetics of schizophrenia to widening our understanding of the inheritance of this illness. Methods: This quasi-experimental study was conducted in Razi psychiatric hospital in Tehran province, Iran. Recruitment of the study samples was conducted in Tehran, Iran, among patients with schizophrenia and their families. For this purpose, individuals with schizophrenia in 40 families with at least 1 to 2 affected members were identified and selected based on a clinical interview conducted by a psychiatrist and according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. The clinical and paraclinical data, drug and substance usage, and medical treatments were collected through a standardized clinical questionnaire. Besides, the Global Assessment Scale and the Positive and Negative Syndrome Scale were completed for all study participants. Results: A total of 22 families had a negative family history, and 1 affected member and the rest of the studied families had a positive family history and at least 2 affected members. In addition, genealogical data (family tree) and lymphoblastic cell categories were developed to examine genes, and subsequent research results will be reported in the future. Conclusion: As the research continues, the approach to sampling must be modified to ensure that the deoxyribonucleic acid bank is as extensively representative as possible of all schizophrenia cases.

Long noncoding RNA polymorphisms and colorectal cancer risk: Progression and future perspectives.

Colorectal cancer (CRC) is one of the most common cancers causing death worldwide. Many long noncoding RNAs (lncRNAs) have possible carcinogenic or tumor suppressor functions. Some lncRNA polymorphisms are useful for predicting cancer risk, and may help advance personalized therapy management. While the use of lncRNAs as biomarkers is promising, there are still drawbacks, and further studies are needed to verify the consistency of current outcomes in large-scale populations and different ethnicities. Single nucleotide polymorphisms (SNPs) can disrupt a lncRNAs' function, thus enhancing or hindering disease occurrence. SNPs can directly influence the lncRNA expression by interfering with transcription factor binding or affecting indirectly a regulatory factors' expression. Moreover, the association between lncRNAs and other RNAs or proteins may be disrupted by SNPs. This research sought to assess the association between lncRNA polymorphisms and CRC risk, as well as clinical and therapeutic consequences in certain cases.

LncRNA polymorphisms and urologic cancer risk.

Urologic cancers involve nearly one-quarter of all cancers and include the prostate, bladder, and kidney cancers. Long non-coding RNAs (LncRNAs) are expressed in a tissue-specific manner and affect cell proliferation, apoptosis, and differentiation. LncRNAs expression is misregulated in urologic cancers, as their aberrant expression may make them capable of being utilized in the diagnosis, prognosis, and treatment of cancers. LncRNAs polymorphisms can affect their structure, expression, and function by interfering with the associated target mRNAs. As a result, lncRNA polymorphisms may be linked to the mechanism driving cancer susceptibility. Therefore, SNPs in lncRNAs may be a beneficial biomarker for early diagnosis and prognosis of cancers, as they affect lncRNA role in tumorigenesis and cancer progression. Moreover, the genetic heredity of lncRNA SNPs affects the personal therapeutic response to drugs. In this study, the lncRNAs polymorphism is summarized in relation to urologic cancers. It is proposed that lncRNA-related polymorphisms, as an individual or combined genotypes, can predict urologic cancer risk, even clinical and prognostic outcomes. However, large-scale population-based prospective studies and comprehensive meta-analyses should be conducted to validate and use these lncRNAs SNPs as the indicators of urologic cancers. Future research should examine the function of these SNPs to explain their associations with urologic cancers.

Suppression of lncRNA NORAD may affect cell migration and apoptosis in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a major malignancy that threatens people's lives worldwide. Long noncoding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) is known to be a potential oncogene in many cancers and may promote cell migration and metastasis, and decrease apoptosis rate. MATERIAL AND METHODS: NORAD expression was measured in 70 pairs of GC tissues and their adjacent normal tissues (ANTs) by quantitative real-time polymerase chain reaction. Si-NORAD gene knockdown study and cellular assays were conducted to assess the correlation between NORAD expression and cell viability, apoptosis, migration, and metastasis. RESULTS: NORAD was significantly overexpressed in GC tissues compared to ANTs (P value < 0.0001). The receiver operating characteristic curve indicated the AUC of 0.721 with the sensitivity and specificity of 78.57 and 61.43, respectively (P value < 0.0001). NORAD downregulation leads to decreased cell viability (P value < 0.001) and migration (P value < 0.01), increased apoptosis rate (P value < 0.0001), and increased protein level for PTEN, E-cadherin, and Bax, but decreased protein level for Bcl-2. CONCLUSION: Generally, NORAD may serve as a potential diagnostic biomarker in GC.

Non-coding RNA-Encoded Peptides/Proteins in Human Cancer: The Future for Cancer Therapy.

Although non-coding RNAs (ncRNAs) were initially thought to be a class of RNA transcripts with no encoding capability, it has been established that some ncRNAs actually contain open reading frames (ORFs), which can be translated into micropeptides or microproteins. Recent studies have reported that ncRNAs-derived micropeptides/ microproteins have regulatory functions on various biological and oncological processes. Some of these micropeptides/microproteins act as tumor inhibitors and some as tumor inducers. Understanding the carcinogenic role of ncRNAs-encoded micropeptides/ microproteins seems to pose potential challenges to cancer research and offer promising practical perspectives on cancer treatment. In this review, we summarized the present information on the association of ncRNAs-derived micropeptides/microproteins with different types of human cancers. We also mentioned their carcinogenic mechanisms in cancer metabolism, signaling pathways, cell proliferation, angiogenesis, metastasis, and so on. Finally, we discussed the potential clinical value of these micropeptides/ microproteins and their potential use in the diagnosis and treatment of cancer. This information may help discover, optimize, and develop new tools based on biological micropeptides/ microproteins for the early diagnosis and development of anticancer drugs.

LncRNA polymorphisms and breast cancer risk.

Breast cancer (BC) is the most prevalent cancer in females and the second reason of cancer-related mortality in females in the world. It is thought to be a complex interaction of variables like personal lifestyle, climate, genetics, and reproductive factors. Many polymorphisms have been linked to cancer in genome-wide association experiments, and they are linked to long non-coding RNAs (lncRNAs). LncRNAs, which have > 200 nucleotides in their transcripts, affect many biological processes, including differentiation, migration, apoptosis, cell cycle, and cell proliferation. Different lncRNAs with tumor suppressor and oncogenic roles have been shown to have elevated expression levels in the development of BC. Single-nucleotide polymorphisms (SNPs) in lncRNAs can affect the expression level, structure, and function of lncRNAs. LncRNA polymorphisms are predictive of cancer incidence, making them useful for early detection and customized therapy control. SNPs may affect genetic susceptibility to BC. This study was set to see whether there was a link between lncRNA polymorphisms and the risk of BC. Accordingly, the individual and combined genotypes of lncRNA-related variants could predict BC and clinical and care outcomes. However, further large-scale trials of diverse ethnic groups and comprehensive health records should be performed to validate the results. Furthermore, adequate functional assessments should be carried out to shed light on the etiology of BC. DATA AVAILABILITY: Not applicable.

Interplay and cooperation of Helicobacter pylori and gut microbiota in gastric carcinogenesis.

Chronic Helicobacter pylori infection is a critical risk factor for gastric cancer (GC). However, only 1-3 % of people with H. pylori develop GC. In gastric carcinogenesis, non-H. pylori bacteria in the stomach might interact with H. pylori. Bacterial dysbiosis in the stomach can strengthen gastric neoplasia development via generating tumor-promoting metabolites, DNA damaging, suppressing antitumor immunity, and activating oncogenic signaling pathways. Other bacterial species may generate short-chain fatty acids like butyrate that may inhibit carcinogenesis and inflammation in the human stomach. The present article aimed at providing a comprehensive overview of the effects of gut microbiota and H. pylori on the development of GC. Next, the potential mechanisms of intestinal microbiota were discussed in gastric carcinogenesis. We also disserted the complicated interactions between H. pylori, intestinal microbiota, and host in gastric carcinogenesis, thus helping us to design new strategies for preventing, diagnosing, and treating GC.

Crosstalk between lncRNAs and miRNAs in gastrointestinal cancer drug resistance.

Gastrointestinal cancers are one of the most prevalent malignancies worldwide. Dysregulation of lncRNAs by epigenetic alteration is crucial in gastrointestinal carcinogenesis. Epigenetic alteration includes DNA methylation, chromatin remodeling, histone modifications, and deregulated-gene expression by miRNAs. LncRNAs are involved in biological processes, including, uncontrolled cell division, migration, invasion, and resistance to apoptosis and drugs. Multiple-drug resistance (MDR) is a crucial obstacle in effective chemotherapy for gastrointestinal cancers. MDR can be associated with the prognosis and diagnosis of patients receiving chemotherapeutic agents (i.e. cisplatin, oxaliplatin, platinum, 5-fluorouracil, gefitinib, methotrexate, taxol, cetuximab, docetaxel, and gemcitabine). In this review, we focused on recently known lncRNAs and their relation with miRNAs and chemotherapeutic drugs, and their modulation in gastrointestinal cancers. Moreover, we mentioned the future prospective and clinical application of lncRNAs as a critical indicator and biomarker in diagnosis, prognosis, staging, grading, and treatment of gastrointestinal cancers.

Emerging therapeutic targets for gastric cancer from a host-Helicobacter pylori interaction perspective.

INTRODUCTION: Gastric cancer (GC) has the higher genetic, cytologic, and architectural heterogeneity compared to other gastrointestinal cancers. By inducing gastric inflammation, Helicobacter pylori (HP) may lead to GC through combining bacterial factors with host factors. In this regard, identification of the major therapeutic targets against the host-HP interactions plays a critical role in GC prevention, diagnosis, and treatment. AREAS COVERED: This study offers new insights into the promising therapeutic targets against the angiogenesis, invasion, or metastasis of GC from a host-HP interaction perspective. To this end, MEDLINE, EMBASE, LILACS, AIM, and IndMed databases were searched for relevant articles since 1992. EXPERT OPINION: Wnt signaling and COX pathway have a well-documented history in the genesis of GC by HP and might be considered as the most promising targets for early GC treatment. Destroying HP may decrease the risk of GC, but it cannot fully hinder the GC development induced by HP infection. Therefore, targeting HP-activated pathways, especially COX-2/Wnt/beta-catenin/VEGF, TLR2/TLR9/COX-2, COX2-PGE2, and NF-κB/COX-2, as well as EPHA2, MMPs, and miR-543/SIRT1 axis, can be an effective measure in the early treatment of GC. However, different clinical trials and large, multi-center cohorts are required to validate these potentially effective targets for GC therapy.