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Nature Communications Oct 2018Circular RNAs (circRNAs) are a large class of transcripts in the mammalian genome. Although the translation of circRNAs was reported, additional coding circRNAs and the...
Circular RNAs (circRNAs) are a large class of transcripts in the mammalian genome. Although the translation of circRNAs was reported, additional coding circRNAs and the functions of their translated products remain elusive. Here, we demonstrate that an endogenous circRNA generated from a long noncoding RNA encodes regulatory peptides. Through ribosome nascent-chain complex-bound RNA sequencing (RNC-seq), we discover several peptides potentially encoded by circRNAs. We identify an 87-amino-acid peptide encoded by the circular form of the long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) that suppresses glioblastoma cell proliferation in vitro and in vivo. This peptide directly interacts with polymerase associated factor complex (PAF1c) and inhibits the transcriptional elongation of multiple oncogenes. The expression of this peptide and its corresponding circRNA are decreased in glioblastoma compared with the levels in normal tissues. Our results establish the existence of peptides encoded by circRNAs and demonstrate their potential functions in glioblastoma tumorigenesis.
Topics: Animals; Carcinogenesis; Cell Cycle; Cell Line; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Nuclear Proteins; Oncogenes; Peptides; RNA; RNA, Circular; RNA, Long Noncoding; Sequence Deletion; Survival Analysis; Tissue Distribution; Transcription Elongation, Genetic; Transcription Factors
PubMed: 30367041
DOI: 10.1038/s41467-018-06862-2 -
Wiley Interdisciplinary Reviews. RNA Jul 2022LINC-PINT is a p53-induced long intergenic noncoding transcript that plays a crucial role in many diseases, especially cancer. This long noncoding RNA (lncRNA) gene... (Review)
Review
LINC-PINT is a p53-induced long intergenic noncoding transcript that plays a crucial role in many diseases, especially cancer. This long noncoding RNA (lncRNA) gene produces in total 102 (LNCipedia) alternatively spliced variants (LINC-PINT:1 to LINC-PINT:102). The functions of known variants include RNA transcripts, host transcripts for circular RNA (circRNA) generation and as sources for the translation of short peptides. In most human tumors, LINC-PINT is down-regulated where it serves as a tumor suppressor. However, the diversity of its functions in other maladies signifies its general clinical importance. Current LINC-PINT molecular functions include RNA-protein interactions, miRNA sponging and epigenetic modulation with these mechanisms operating in different cellular contexts to exert effects on biological processes ranging from DNA damage responses, cell cycle and growth arrest, senescence, cell migration and invasion, and apoptosis. Genetic polymorphisms in LINC-PINT have also been functionally associated with cancer and other pathologies including the autoimmune diseases pemphigus foliaceus and arthritis. Hence, LINC-PINT shows great potential as a clinical biomarker, especially for the diagnosis and prognosis of cancer. In this review, we explore the current knowledge highlighting the distinctive molecular functions of LINC-PINT in specific cancers and other disease states. This article is categorized under: RNA in Disease and Development > RNA in Disease.
Topics: Cell Cycle; Cell Movement; Disease; Genes, p53; Humans; MicroRNAs; Neoplasms; RNA, Long Noncoding
PubMed: 35019222
DOI: 10.1002/wrna.1705 -
Trends in Cognitive Sciences Apr 2018Until recently, many psychologists were skeptical that young children cared about reputation. New evidence suggests that by age five, children begin to understand the... (Review)
Review
Until recently, many psychologists were skeptical that young children cared about reputation. New evidence suggests that by age five, children begin to understand the broad importance of reputation and to engage in surprisingly sophisticated impression management. These findings prompt exciting new questions about the development of a fundamental social competency.
Topics: Child; Child Behavior; Child Development; Child, Preschool; Humans; Interpersonal Relations; Social Behavior; Social Perception
PubMed: 29571663
DOI: 10.1016/j.tics.2018.01.006 -
The Journal of Pediatrics Sep 2006To determine whether extremely low birth weight infants (ELBW) transfused at lower hemoglobin thresholds versus higher thresholds have different rates of survival or... (Randomized Controlled Trial)
Randomized Controlled Trial
The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants.
OBJECTIVE
To determine whether extremely low birth weight infants (ELBW) transfused at lower hemoglobin thresholds versus higher thresholds have different rates of survival or morbidity at discharge.
STUDY DESIGN
Infants weighing <1000 g birth weight were randomly assigned within 48 hours of birth to a transfusion algorithm of either low or high hemoglobin transfusion thresholds. The composite primary outcome was death before home discharge or survival with any of either severe retinopathy, bronchopulmonary dysplasia, or brain injury on cranial ultrasound. Morbidity outcomes were assessed, blinded to allocation.
RESULTS
Four hundred fifty-one infants were randomly assigned to low (n = 223) or high (n = 228) hemoglobin thresholds. Groups were similar, with mean birth weight of 770 g and gestational age of 26 weeks. Fewer infants received one or more transfusions in the low threshold group (89% low versus 95% high, P = .037). Rates of the primary outcome were 74.0% in the low threshold group and 69.7% in the high (P = .25; risk difference, 2.7%; 95% CI -3.7% to 9.2%). There were no statistically significant differences between groups in any secondary outcome.
CONCLUSIONS
In extremely low birth weight infants, maintaining a higher hemoglobin level results in more infants receiving transfusions but confers little evidence of benefit.
Topics: Algorithms; Anemia; Erythrocyte Transfusion; Hemoglobins; Hospital Mortality; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Treatment Outcome
PubMed: 16939737
DOI: 10.1016/j.jpeds.2006.05.011 -
Seminars in Cancer Biology May 2021Cancer persists as a major health catastrophe and a leading cause of widespread mortality across every nation. Research of several decades has increased our... (Review)
Review
Cancer persists as a major health catastrophe and a leading cause of widespread mortality across every nation. Research of several decades has increased our understanding of the pivotal pathways and key players of the host during tumor development and progression, which has enabled generation of precision therapeutics with improved efficacy. Despite such tremendous advancements in our combat against this fatal disease, a majority of the cancer patients suffer from poor tumor- free survival owing to the increased incidence of recurrent tumor. This is primarily due to the development of resistance against contemporary anti- cancer strategies. Recent studies have pointed towards the involvement of the human symbiotic gut microbiota in regulating the outcome of chemotherapy and immunotherapy. It does so primarily by modulating the metabolism of the drugs and host immune response, thereby enhancing the efficacy and ameliorating the toxicity. The interactions between the therapeutic agents, microbial community and host immunity may provide a new avenue for the clinical management of cancer. In addition, consumption of dietary pro-, pre- and synbiotics has been recognized to confer protection against tumor genesis and also promote improved response to traditional tumor suppressive strategies. Naturally, the use of various combinatorial regimes containing dietary supplements that improve the gut microbiome in amalgamation with conventional cancer treatment methods may significantly augment the therapeutic outcome of cancer patients and circumnavigate the resistance mechanisms that confound traditional therapies. In this review, we have summarized the role of the gut microbiome, which is the largest assembly of commensals within the human body, in regulating the efficacy and toxicity of various existing anti- cancer therapies including chemotherapy, immunotherapy and surgery. Furthermore, we have discussed how novel strategies integrating the application of probiotics, prebiotics, synbiotics and antibiotics in combination with the aforementioned anti- cancer modules manipulate the gut microbiota and, therefore, augment their therapeutic outcome. Together, such innovative anti- tumorigenic approaches may prove highly effective in improving the prognosis of cancer patients.
Topics: Animals; Antineoplastic Agents; Gastrointestinal Microbiome; Humans; Neoplasms; Prebiotics
PubMed: 32739479
DOI: 10.1016/j.semcancer.2020.07.012 -
Cancer Management and Research 2021This study mainly explored the expression level of LINC-PINT in bladder cancer and its relationship with prognosis. Meanwhile, the effect of LINC-PINT on the biological...
BACKGROUND
This study mainly explored the expression level of LINC-PINT in bladder cancer and its relationship with prognosis. Meanwhile, the effect of LINC-PINT on the biological function of bladder cancer was also explored.
METHODS
The expression levels of LINC-PINT and miR-155-5p were detected by qRT-PCR. The prognostic significance of LINC-PINT in bladder cancer was studied by the Kaplan-Meier curve and Log rank test. CCK-8 and Transwell assays were used to analyze the proliferation, migration, and invasion ability. The targeting relationship between LINC-PINT and miR-155-5p was analyzed using bioinformatics and dual-luciferase reporter assays.
RESULTS
The expression of LINC-PINT was downregulated in bladder cancer tissues and cell lines, and miR-155-5p showed the opposite trend in bladder cancer tissues. Kaplan-Meier curve proved that the patients with low LINC-PINT expression had a lower five-year survival rate and the Log rank test displayed that LINC-PINT was a prognostic factor of BC. CCK-8 and Transwell results showed that LINC-PINT could inhibit the ability of proliferation, migration, and invasion. LINC-PINT was proved to target miR-155-5p in bladder cancer. Dual-luciferase reporter gene assay showed that the relative luciferase activity of overexpression miR-155-5p co-transfected with LINC-PINT-wt was significantly lower. LINC-PINT was negatively correlated with miR-155-5p.
CONCLUSION
LINC-PINT is a potential prognostic marker of bladder cancer, and the up-regulation of Lin-PINT can inhibit the proliferation, invasion, and migration of bladder cancer cells by targeting miR-155-5p.
PubMed: 34103994
DOI: 10.2147/CMAR.S305547 -
Cell Biochemistry and Function Dec 2020LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of...
LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of ovarian cancer (OC). LINC-PINT expression level in different FIGO stages of OC and its adjacent tissues, normal HOSE and OC cell lines (A2780, SKOV3, OVCAR3 and HO-8910) was determined by qRT-PCR. Survival analysis on LINC-PINT and OC patients was conducted by Kaplan-Meier. CCK-8, flow cytometry, wound-healing, Transwell assays and western blot were performed to detect the effects of LINC-PINT on proliferation, apoptosis, migration, invasion and EMT process in OC cells. Target gene of LINC-PINT was predicted by Starbase and verified by dual-luciferase reporter assay. The expression of miR-374a-5p in normal and OC tissues, LINC-PINT- or siLINC-PINT-modified OC cells was determined. Moreover, rescue assay was carried out to confirm whether LINC-PINT contributes to the development of OC cells through targeting miR-374a-5p. Low expression of LINC-PINT was observed in OC tissues and cells, noticeably, LINC-PINT expression was even lower in OC tissues with higher FIGO stage. Increased LINC-PINT expression significantly inhibited cell proliferation, promoted apoptosis and suppressed migration, invasion and EMT process, while silencing of LINC-PINT caused the opposite results. Moreover, LINC-PINT sponged miR-374a-5p and overexpressed miR-374a-5p attenuated the effect of up-regulated LINC-PINT on cell viability, migration, invasion and apoptosis. LINC-PINT acts as a tumour suppressor, as it could inhibit cell proliferation, migration, invasion and EMT process, and promote cell apoptosis through down-regulating miR-374a-5p. SIGNIFICANCE OF THE STUDY: Ovarian cancer (OC), which is a frequently diagnosed tumour in female reproductive organs, has a high incidence rate behind cervical cancer and endometrial cancer. LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of ovarian cancer (OC) and found that LINC-PINT inhibited cell proliferation, migration invasion and EMT process of OC cell via regulating miR-374a-5p; it might be a potential target for OC treatment.
Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; MicroRNAs; Neoplasm Invasiveness; Ovarian Neoplasms; RNA, Long Noncoding; RNA, Neoplasm
PubMed: 32638404
DOI: 10.1002/cbf.3565 -
Biomedicine & Pharmacotherapy =... Nov 2021Cancer involves complex etiology factors, multiple stages, and intricate gene mutations. Long non-coding RNAs (lncRNAs) are implicated as molecular mechanisms underlying... (Review)
Review
Cancer involves complex etiology factors, multiple stages, and intricate gene mutations. Long non-coding RNAs (lncRNAs) are implicated as molecular mechanisms underlying human genomic activity in various physiologic and pathophysiologic conditions. However, the sophisticated modifications and regulatory processes linking lncRNAs to cancer initiation and progression have not yet been fully explored. Long intragenic non-coding RNA p53-induced transcript (LINC-PINT) is an lncRNA that functions as a tumor suppressor gene involved in various tumors and malignant activities. LINC-PINT is downregulated in nasopharyngeal cancer, renal carcinoma, non-small cell lung cancer, glioblastoma, thyroid cancer, retinoblastoma, ovarian cancer, breast cancer, esophageal squamous cell carcinoma, osteosarcoma, melanoma, and gastric cancer. Furthermore, decreased LINC-PINT expression predicts poor prognosis and advanced clinical tumor stages. Together, these studies indicate that LINC-PINT could serve as a diagnostic and prognostic indicator in cancer. The specific lncRNA regulatory mechanism of LINC-PINT may also be a novel target for cancer therapies.
Topics: Animals; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; RNA, Long Noncoding; Signal Transduction
PubMed: 34474342
DOI: 10.1016/j.biopha.2021.112127 -
Frontiers in Molecular Biosciences 2023Long noncoding RNAs (lncRNAs) possess the potential for therapeutic targeting to treat many disorders, including cancers. Several RNA-based therapeutics (ASOs and small...
Long noncoding RNAs (lncRNAs) possess the potential for therapeutic targeting to treat many disorders, including cancers. Several RNA-based therapeutics (ASOs and small interfering RNAs) have gained FDA approval over the past decade. And with their potent effects, lncRNA-based therapeutics are of emerging significance. One important lncRNA target is LINC-PINT, with its universalized functions and relationship with the famous tumor suppressor gene Establishing clinical relevance, much like p53, the tumor suppressor activity of LINC-PINT is implicated in cancer progression. Moreover, several molecular targets of LINC-PINT are directly or indirectly used in routine clinical practice. We further associate LINC-PINT with immune responses in colon adenocarcinoma, proposing the potential utility of LINC-PINT as a novel biomarker of immune checkpoint inhibitors. Collectively, current evidence suggests LINC-PINT can be considered for use as a diagnostic/prognostic marker for cancer and several other diseases.
PubMed: 37006616
DOI: 10.3389/fmolb.2023.1097694 -
Cell Death & Disease May 2021Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and...
Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.
Topics: Cell Line, Tumor; Cell Proliferation; DNA Damage; DNA Repair; DNA-Activated Protein Kinase; Humans; Nasopharyngeal Neoplasms; RNA, Long Noncoding
PubMed: 33963177
DOI: 10.1038/s41419-021-03728-2