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.

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.

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.

Oral microbiota and Helicobacter pylori in gastric carcinogenesis: what do we know and where next?

Gastric cancer (GC) is one of the most common malignancies causing death worldwide, and Helicobacter pylori is a powerful inducer of precancerous lesions and GC. The oral microbiota is a complex ecosystem and is responsible for maintaining homeostasis, modulating the immune system, and resisting pathogens. It has been proposed that the gastric microbiota of oral origin is involved in the development and progression of GC. Nevertheless, the causal relationship between oral microbiota and GC and the role of H. pylori in this relationship is still controversial. This study was set to review the investigations done on oral microbiota and analyze various lines of evidence regarding the role of oral microbiota in GC, to date. Also, we discussed the interaction and relationship between H. pylori and oral microbiota in GC and the current understanding with regard to the underlying mechanisms of oral microbiota in carcinogenesis. More importantly, detecting the patterns of interaction between the oral cavity microbiota and H. pylori may render new clues for the diagnosis or screening of cancer. Integration of oral microbiota and H. pylori might manifest a potential method for the assessment of GC risk. Hence it needs to be specified the patterns of bacterial transmission from the oral cavity to the stomach and their interaction. Further evidence on the mechanisms underlying the oral microbiota communities and how they trigger GC may contribute to the identification of new prevention methods for GC. We may then modulate the oral microbiota by intervening with oral-gastric bacterial transmission or controlling certain bacteria in the oral cavity.

Helicobacter pylori virulence factors in relation to gastrointestinal diseases in Iran.

PURPOSES: Helicobacter pylori as an important pathogenic bacterium that colonizes in gastric mucosa, is one of the causative agents in development of some types of gastric diseases, such as chronic active gastritis, peptic ulcer disease (PUD) and gastric cancer (GC). In this review, the aim is studying different genotypes of H. pylori, and the extent of their participation in the pathogenesis of this bacterium which creates gastroduodenal disorders. RESULTS: Some genotypes of H. pylori have a major role in creation of gastroduodenal diseases, whereas some other genotypes of the bacterium do not cause gastric diseases in Iran. It was also reported that some genotypes of this bacterium in different conditions and among different ethnic groups demonstrate different effectiveness. CONCLUSION: Role of genotypes of H. pylori in creation of gastroduodenal diseases is different among various regions and ethnic groups of Iran.

Helicobacter pylori genotypes determine risk of non-cardia gastric cancer and intestinal- or diffuse-type GC in Ardabil: A very high-risk area in Northwestern Iran.

Frequency of the Helicobacter pylori vacA gene polymorphism and its association with gastric cancer (GC) was assessed in Ardabil, a very high-risk area in Northwestern Iran. We determined the presence of the H. pylori 16S rDNA gene and the vacA s-, m-, i-, and d-region genotypes in DNA from fresh gastric biopsies. Patients with GC were classified based on both the anatomic site and the histopathologic type of tumor Of 135 patients, including 57 with non-atrophic gastritis (NAG) and 78 with GC, 103 were infected by H. pylori. The vacA i1 and d1 genotypes were significantly linked to an increased risk of GC, where both cardia (CGC) and non-cardia GC (NCGC) patients were entered into the analysis. The adjusted OR was 9.59 for i1 and 4.39 for d1. Furthermore, i1 was significantly linked to an increased risk of the intestinal-type adenocarcinoma (OR = 14.04) and d1 to the risk of the diffuse-type adenocarcinoma (OR = 7.71). The presence of the m1-type of vacA in combination with i1 or d1 further increased the risk of GC. When the analysis was restricted to NCGC, the adjusted OR for i1 and d1, was 37.52 and 7.17, respectively. No significant association was found between genotypes and the risk of GC in the cardia site of the stomach. It is proposed that the new types of H. pylori vacA, i1 and d1, might be important determinants of NCGC risk in Ardabil. The m1, not independently, but in combination might further define the risk of GC. i1and d1 might also predict the risk of the intestinal- and diffuse-type adenocarcinomas, respectively.

Relevance of Helicobacter pylori vacA 3'-end Region Polymorphism to Gastric Cancer.

BACKGROUND: Helicobacter pylori vacA genotypes play an important role in the pathogenesis of severe gastrointestinal disease. MATERIALS AND METHODS: We identified a novel polymorphic site in the 3'-end region of H. pylori vacA gene, denoted by c1/-c2 (c1: with deletion of 15 bp), and examined associations of this and the previous four sites as well as cagA status with gastroduodenal diseases, in a total of 217 Iranian H. pylori isolates. Histopathologic evaluations were performed and patients with gastric cancer (GC) were further classified based on the anatomic site of tumor, including cardia and noncardia GC, and the histopathologic type of tumor, including intestinal- and diffuse-type GC. RESULTS: The vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with an increased risk of GC, the odds ratio (95% confidence interval) was 4.29 (2.03-9.08), 6.11 (2.63-14.19), 3.18 (1.49-6.76), 15.13 (5.86-39.01), and 2.59 (1.09-6.12), respectively. The vacA c1 genotype had an increased age- and sex-adjusted risk for GC by the multiple logistic regression analysis; the OR was 38.32 (95% CI, 6.60-222.29). This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. No significant correlation was found between s1, whether independently or in combination, and the risk of GC or peptic ulcer disease (PUD). The vacA i1 and cagA genotypes were linked to an increased risk of PUD; the OR (95% CI) was 2.80 (1.45-5.40) and 2.62 (1.23-5.61), respectively. The presence of both the vacA i1 and cagA genotypes further increased the risk of PUD; the OR was 5.20 (95% CI, 1.92-14.03). CONCLUSION: The H. pylori vacA c1 genotype might therefore be one of the strongest risk predictors of GC in male patients aged ≥55 in Iran.

Helicobacter pylori vacuolating cytotoxin genotypes and preneoplastic lesions or gastric cancer risk: a meta-analysis.

BACKGROUND AND AIM: Disease progression to gastric cancer (GC) occurs in only a small proportion of Helicobacter pylori (H. pylori) infected patients. The bacterium vacuolating cytotoxin A (vacA) gene polymorphisms may determine the clinical consequences. We examined the strength of this association in adult-infected populations and modeled the impact of mean age-standardized incidence rates (ASRs) of GC as a hypothesized moderator variable. METHODS: Pooled relative risk (RR) estimates were calculated. Subgroup, sensitivity, and meta-regression analyses were conducted. RESULTS: Totally, 33 studies (1446 cases/2697 controls) were analyzed. The vacA-s1 genotype was significantly associated with an increased risk of atrophic gastritis(AG), intestinal metaplasia(IM), and GC (RR = 1.116, 95% CI, 1.019-1.222; RR = 1.418, 95% CI, 1.035-1.942; and RR = 1.333, 95% CI, 1.115-1.593, respectively); however, the vacA m1 genotype strongly increased the risk of IM and GC, but not AG (RR = 1.571, 95% CI, 1.247-1.980 and RR = 1.431, 95% CI, 1.180-1.735, respectively). The vacA s1m1 allelic combination was linked to an increased risk of GC. The m1-type of vacA was more potent than s1 for predicting the risk of GC within the subgroups with the mean ASRs of 11/100,000-19/100,000 and less than 10/100,000. The meta-regression analysis indicated that the ASR of GC modified the association between H. pylori genotypes and GC risk, where the estimated risk was significantly decreased with increasing the mean ASRs of GC (P-values = 0.025, 0.00009, and 0.0005 for s1, m1, and s1m1, respectively). CONCLUSIONS: The H. pylori vacA-s1 and vacA-m1 allelic variants strongly increased susceptibility to IM and GC; however, only s1 showed an association with AG. These associations were largely influenced by geographic variations in the GC incidence rate.

Multiple repeats of Helicobacter pylori CagA EPIYA-C phosphorylation sites predict risk of gastric ulcer in Iran.

Biological activity of Helicobacter pylori oncoprotein CagA is determined by a diversity in the tyrosine phosphorylation motif sites. In the present study, the diversity and the type of the H. pylori CagA EPIYA motifs and their association with gastric ulcer (GU) and duodenal ulcer (DU) in Iranian dyspeptic patients were assessed. PCR amplification, sequencing, and bioinformatic analysis were performed to determine the pattern of CagA EPIYA motifs. Of 168 H. pylori cagA(+) strains, the frequency of ABC was 93.50%, ABCCC 5.40%, ABC + ABCCC 0.6% and ABCC 0.6%. There was no EPIYA-D segment. The ABCCC pattern of EPIYA motif was more frequent in the H. pylori isolates from GU (8/50, 16%) than in those from chronic gastritis (CG) (0/81, 0%) (P = 0). In contrast, The ABC pattern of EPIYA motif was less frequent in the H. pylori isolates from GU (41/50, 82%) than in those from CG (80/81, 98.80%) (Age-sex-adjusted odds ratio (OR) = 0.020, 95% CI = 0.002-0.259; P = 0.003). The distribution of the ABC motif was almost the same in H. pylori isolates from CG (98.80%) and DU diseases (97.30%). There was no significant association between the number of CagA EPIYA-C segment and DU (P > 0.05). We have proposed that CagA from Iranian H. pylori strains were Western type and all strains had active phosphorylation sites. The three EPIYA-C motifs of CagA were more frequently observed in the H. pylori strains from GU; thus it might be an important biomarker for predicting the GU risk in Iran.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.