LncRNAs-circRNAs as Rising Epigenetic Binary Superstars in Regulating Lipid Metabolic Reprogramming of Cancers.

As one of novel hallmarks of cancer, lipid metabolic reprogramming has recently been becoming fascinating and widely studied. Lipid metabolic reprogramming in cancer is shown to support carcinogenesis, progression, distal metastasis, and chemotherapy resistance by generating ATP, biosynthesizing macromolecules, and maintaining appropriate redox status. Notably, increasing evidence confirms that lipid metabolic reprogramming is under the control of dysregulated non-coding RNAs in cancer, especially lncRNAs and circRNAs. This review highlights the present research findings on the aberrantly expressed lncRNAs and circRNAs involved in the lipid metabolic reprogramming of cancer. Emphasis is placed on their regulatory targets in lipid metabolic reprogramming and associated mechanisms, including the clinical relevance in cancer through lipid metabolism modulation. Such insights will be pivotal in identifying new theranostic targets and treatment strategies for cancer patients afflicted with lipid metabolic reprogramming.

Lumbosacral Paravertebral Tophaceous Gout on an Adolescent Mimicking Malignant Neoplasm in 18 F-FDG PET/CT.

ABSTRACT: Contrast-enhanced MRI was performed on a 17-year-old adolescent boy with chronic lumbar and lower-limb pain, which had worsened over the past 3 days. It revealed a suspicious malignant mass adjacent to right appendage of L5-S1 vertebrae, with mixed signals and heterogeneous and obvious enhancement. 18 F-FDG PET/CT was subsequently performed for staging. It showed an FDG-avid mass with mixed density in right psoas major muscle, involving adjacent appendage of L5-S1 vertebrae. Histopathological examination confirmed the mass to be gouty tophus, characterized by nodular homogeneous pink amorphous deposits around the cartilage tissue, surrounded by histiocytes and multinucleated giant cells.

Low­dose ionizing radiation attenuates high glucose­induced hepatic apoptosis and immune factor release via modulation of a miR­155­SOCS1 axis.

Diabetic liver injury (DLI) can result in several diseases of the liver, including steatohepatitis, liver fibrosis, cirrhosis, and liver cancer. Low­dose ionizing radiation (LDIR) has hormetic effects in normal/disease conditions. However, whether LDIR has a beneficial effect on DLI has not been assessed previously. MicroRNA (miR)­155 and its target gene suppressor of cytokine signaling 1 (SOCS1) play critical roles in modulating hepatic proliferation, apoptosis, and immunity. However, whether a miR­155­SOCS1 axis is involved in high glucose (HG) induced hepatic damage remains to be determined. In the present study, mouse hepatocyte AML12 cells were treated with 30 mM glucose (HG), 75 mGy X­ray (LDIR), or HG plus LDIR. The expression levels of miR­155 and SOCS1 were determined by reverse transcription­quantitative PCR and western blotting. Additionally, apoptosis was measured using flow cytometry. The release of inflammatory factors, including TNF­α, IL­1ß, IL­6, IL­10, and IFN­Î³, after HG and/or LDIR treatment was detected by ELISA. The results showed that HG may induce hepatic apoptosis by upregulating the levels of miR­155 and downregulating the levels of SOCS1. HG also stimulated the secretion of TNF­α, IL­1ß, IL­6, and IL­10. However, LDIR blocked the HG­induced activation of a miR­155­SOCS1 axis and suppressed the release of inflammatory factors. These results indicated that a miR­155­SOCS1 axis plays a role in HG­induced liver injury, and LDIR may exert a hepatoprotective effect by regulating the miR­155­SOCS1 axis.

Application of thyroglobulin and anti-thyroglobulin antibody combined with emission computed tomography in the adjuvant diagnosis of differentiated thyroid carcinoma.

PURPOSE: Thyroid nodules are a kind of common endocrine system disease, with approximately 5% of them developing into malignant lesions, the most common of which belong to differentiated thyroid carcinoma (DTC). Accurate differential diagnosis using reliable methods and targeted treatment of benign and malignant thyroid nodules are of great significance to improve patient outcomes. This study mainly investigates the diagnostic value of thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-TgAb) combined with emission computed tomography (ECT) in the adjuvant diagnosis DTC. METHODS: All the data of 387 histopathologically diagnosed DTC patients (observation group) and 151 patients with nodular goiter (control group) admitted between June 2019 and June 2021 were collected and retrospectively analyzed. Serum Tg and anti-TgAb levels were detected in all subjects. In addition, all patients in the observation group underwent thyroid ECT, and the results were compared with the pathological findings. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic performance of Tg, TgAb and thyroid ECT, either alone or in combination, in patients with thyroid cancer (TC). RESULTS: The consistency test showed that Tg (Kappa-value = 0.370) and anti-TgAb (Kappa-value = 0.393) had generally consistent efficiency with pathological findings in the diagnosis of DTC; ECT (Kappa-value = 0.625) and the combined diagnosis of the three (Kappa-value = 0.757) showed higher consistency than the pathological diagnosis, of which the combined diagnosis contributed to an even higher consistency. The combined diagnosis of Tg, anti-TgAb, and thyroid ECT outperformed either of these alone in DTC diagnosis, with a sensitivity of 91.5%, a specificity of 86.1%, and an accuracy of 90%. CONCLUSIONS: The combination of Tg. anti-TgAb, and RNI can effectively improve the diagnostic accuracy of DTC and reduce the missed diagnosis rate, which has important reference significance for clinical diagnosis and treatment of TC.

Multiple-Organ Involvement of Malakoplakia Mimicking Malignant Neoplasms on 18 F-FDG PET/CT.

ABSTRACT: Abdominal contrast-enhanced CT was performed in a 61-year-old man with difficulties of urination and defecation for 4 months, which revealed huge rectal masses involving multiple adjacent organs, suspected as malignant lesions. 18 F-FDG PET/CT was subsequently performed for staging. The images showed intense FDG uptake and slightly hyperdense masses involving rectum, bladder, prostate, left ureter, and the anterior abdominal wall at the level of the pelvic cavity. Histopathological examination confirmed the masses were due to malakoplakia, which displayed as abundant von Hansemann cells aggregated and infiltrated in lesions, with distinctive cytoplasmic inclusions termed Michaelis-Gutmann bodies.

Hypoxia-responsive circRNAs: A novel but important participant in non-coding RNAs ushered toward tumor hypoxia.

Given the rapid developments in RNA-seq technologies and bioinformatic analyses, circular RNAs (circRNAs) have gradually become recognized as a novel class of endogenous RNAs, characterized by covalent loop structures lacking free terminals, which perform multiple biological functions in cancer genesis, progression and metastasis. Hypoxia, a common feature of the tumor microenvironments, profoundly affects several fundamental adaptive responses of tumor cells by regulating the coding and non-coding transcriptomes and renders cancer's phenotypes more aggressive. Recently, hypoxia-responsive circRNAs have been recognized as a novel player in hypoxia-induced non-coding RNA transcriptomics to modulate the hypoxic responses and promote the progression and metastasis of hypoxic tumors. Moreover, via extracellular vesicles-exosomes, these hypoxia-responsive circRNAs could transmit hypoxia responses from cancer cells to the cells of surrounding matrices, even more distant cells of other organs. Here, we have summarized what is known about hypoxia-responsive circRNAs, with a focus on their interaction with hypoxia-inducible factors (HIFs), regulation of hypoxic responses and relevance with malignant carcinoma's clinical features, which will offer novel insights on the non-coding RNAs' regulation of cancer cells under hypoxic stress and might aid the identification of new theranostic targets and define new therapeutic strategies for those cancer patients with resistance to radiochemotherapy, because of the ubiquity of tumoral hypoxia.

Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network.

BACKGROUND: A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in the Oct4 promoter. RESULTS: We identify Platr10 as an Oct4 - Sox2 binding lncRNA that is activated in somatic cell reprogramming. Platr10 is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressed Platr10 functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show that Platr10 interacts with multiple pluripotency-associated genes, including Oct4, Sox2, Klf4, and c-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate that Platr10 helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show that Platr10 contains an Oct4 binding element that interacts with the Oct4 promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishes Platr10 activity. CONCLUSION: These data suggest that Platr10 functions as a novel chromatin RNA molecule to control pluripotency in trans by modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network.

Aberrant shuttling of long noncoding RNAs during the mitochondria-nuclear crosstalk in hepatocellular carcinoma cells.

There is intense crosstalk between mitochondria and the nucleus that is mediated by proteins and long noncoding RNAs (lncRNAs). Using a modified RNA fluorescent in situ hybridization (RNA-FISH) assay coupled with MitoTracker staining, we tracked the mitochondrial localization of lncRNAs, including lncND6 and lncCytB. The nuclear genome-transcribed lncRNA MALAT1 was enriched in the mitochondria of hepatocellular carcinoma cells. Knockdown of MALAT1 significantly impaired mitochondrial function and alter tumor phenotype in HepG2 cells. The localization of the mitochondria-encoded lncRNA lncCytB was also abnormal in HepG2 cells. In normal hepatic HL7702 cells, lncCytB was located in mitochondria, but in HepG2 cells, it was enriched considerably in the nucleus. These data suggest that aberrant shuttling of lncRNAs, whether nuclear genome-encoded or mitochondrial genome-transcribed, may play a critical role in abnormal mitochondrial metabolism in cancer cells. This data lays the foundation for further clarifying the roles of mitochondria-associated lncRNAs in cancers.

Case report of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography imaging of a patient with multiple endocrine gland metastases from small cell lung cancer.

Synchronous multiple endocrine gland metastasis caused by small cell lung cancer (SCLC) is rare. A patient was investigated for primary cancer because of suspected brain metastasis on computed tomography (CT). Baseline 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT was positive in the lung and multiple endocrine glands (right thyroid, right breast, pancreatic body, right adrenal gland, and left ovary). Histopathology confirmed small cell lung cancer. The patient's symptoms were alleviated after chemotherapy and brain radiotherapy. Follow-up PET-CT revealed that some of the lesions had disappeared and some had reduced in size. This rare case of multiple endocrine gland metastases from SCLC suggests that whole body PET-CT is a useful tool to detect rare/asymptomatic metastases.

Discriminant function analysis of the occurrence risk of abnormal electrocardiogram in thyroidectomized differentiated thyroid carcinoma patients with short-term overt hypothyroidism.

OBJECTIVES: The common form and risk factors of electrocardiogram (ECG) abnormality in thyroidectomized differentiated thyroid carcinoma (DTC) patients with short-term overt hypothyroidism were investigated and some discriminant formulas for forecasting the occurrence of abnormal ECG in this specific population were deduced in this study. METHODS: A total of 260 thyroidectomized DTC patients were retrospectively reviewed, 67 of whom had abnormal ECG and 193 normal ECG after short-term (3 weeks) levothyroxine (L-T4) withdrawal. One-way ANOVA, Spearman's rank correlation analysis and discriminant function analysis were performed using data from these DTC patients. RESULTS: A flat or inverted T wave in inferior myocardial and left ventricular wall leads was the most common abnormal ECG finding in short-term overt hypothyroidism. Statistical analyses showed that age, interval, TSH-end (The serum hormothyrin level at the end of L-T4 withdrawal for 3 weeks), and TSH-vel (The average ascending velocity of serum hormothyrin level during L-T4 withdrawal for 3 weeks) were statistically significant and positively correlated with the occurrence of abnormal ECG. Meanwhile, TSH-vel showed the highest correlation coefficient (r = 0.358, p = 0.000). The formulas, especially deduced from age, interval and TSH-vel, could discriminate patients with abnormal ECG or not as high as 77.6 and 70.5%, respectively (resubstitution accuracy: 72.3%). CONCLUSION: The thyroidectomized DTC patients undergoing short-term L-T4 withdrawal before their first radioiodine ablative therapy, who had one or more of the above-mentioned risk factors, are likely to show abnormal ECG findings. The formulas from discriminant function analysis may be helpful for predicting patients with abnormal ECG with short-term L-T4 withdrawal and allow appropriate medical intervention beforehand.

Sex determination from the mandibular ramus flexure of Koreans by discrimination function analysis using three-dimensional mandible models.

It has been known that mandible ramus flexure is an important morphologic trait for sex determination. However, it will be unavailable when mandible is incomplete or fragmented. Therefore, the anthropometric analysis on incomplete or fragmented mandible becomes more important. The aim of this study is to investigate the sex-discriminant potential of mandible ramus flexure on the Korean three-dimensional (3D) mandible models with anthropometric analysis. The sample consists of 240 three dimensional mandibular models obtained from Korean population (M:F; 120:120, mean age 46.2 y), collected by The Catholic Institute for Applied Anatomy, The Catholic University of Korea. Anthropometric information about 11 metric was taken with Mimics, anthropometry libraries toolkit. These parameters were subjected to different discriminant function analyses using SPSS 17.0. Univariate analyses showed that the resubstitution accuracies for sex determination range from 50.4 to 77.1%. Mandibular flexure upper border (MFUB), maximum ramus vertical height (MRVH), and upper ramus vertical height (URVH) expressed the greatest dimorphism, 72.1 to 77.1%. Bivariate analyses indicated that the combination of MFUB and MRVH hold even higher resubstitution accuracy of 81.7%. Furthermore, the direct and stepwise discriminant analyses with the variables on the upper ramus above flexure could predict sex in 83.3 and 85.0%, respectively. When all variables of mandibular ramus flexure were input in stepwise discriminant analysis, the resubstitution accuracy arrived as high as 88.8%. Therefore, we concluded that the upper ramus above flexure hold the larger potentials than the mandibular ramus flexure itself to predict sexes, and that the equations in bivariate and multivariate analysis from our study will be helpful for sex determination on Korean population in forensic science and law.

Low-dose radiation-induced responses: focusing on epigenetic regulation.

PURPOSE: With the widespread use of ionising radiation, the risks of low-dose radiation have been increasingly highlighted for special attention. This review introduces the potential role of epigenetic elements in the regulation of the effects of low-dose radiation. MATERIALS AND METHODS: The related literature has been analysed according to the topics of DNA methylation, histone modifications, chromatin remodelling and non-coding RNA modulation in low-dose radiation responses. RESULTS: DNA methylation and radiation can reciprocally regulate effects, especially in the low-dose radiation area. The relationship between histone methylation and radiation mainly exists in the high-dose radiation area; histone deacetylase inhibitors show a promising application to enhance radiation sensitivity, both in the low-dose and high-dose areas; phosphorylated histone 2 AX (H2AX) shows a low sensitivity with 1-15 Gy irradiation as compared with lower dose radiation; and histone ubiquitination plays an important role in DNA damage repair mechanisms. Moreover, chromatin remodelling has an integral role in the repair of DNA double-strand breaks and the response of chromatin to ionising radiation. Finally, the effect of radiation on microRNA expression seems to vary according to cell type, radiation dose, and post-irradiation time point. CONCLUSION: Small advances have been made in the understanding of epigenetic regulation of low-dose radiation responses. Many questions and blind spots deserve to be investigated. Many new epigenetic elements will be identified in low-dose radiation responses, which may give new insights into the mechanisms of radiation response and their exploitation in radiotherapy.

Approach to radiation therapy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the 5th most common cancer and the third most common cause of cancer-related death in the world with an estimated incidence of approximately 1 million new cases annually, has becoming a major global health problem in the world. A variety of treatment modalities, including resection, liver transplantation, transarterial chemoembolization (TACE), local ablative therapy and radiation therapy (RT) have been reported. Although partial hepatectomy and liver transplantation may offer the best chance of cure, only 15% of the patients have the chance to be treated by surgery when diagnosed. The effectiveness of systemic chemotherapy for HCC has been minimal, and local ablative therapy may offer comparable survival in patients with small HCC and preserve liver function. Recently, with developments in radiotherapy techniques, radiotherapy has been shown to play potential roles in a wide spectrum of HCC and to become more important so that it is necessary to evaluate the effect of radiotherapy in treatment of HCC. This paper is aiming mainly at the current radiation therapy strategies and their current advances, the optimal radiation therapy strategies will complement the current treatments and improve the treatment efficiency.