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HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA (lncRNA) which is increasingly being perceived as a tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation of target gene expression carried out by HOTAIR is thorough modulation of chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and histone demethylase lysine-specific demethylase 1 (LSD1). Incidentally, HOTAIR was the first lncRNA shown to elicit sponging of specific microRNA (miRNA or miR) species in a trans-acting manner. It has been extensively studied in various cancers, including gliomas and is regarded as a prominent pro-tumorigenic and pro-oncogenic lncRNA. Indeed, the expression of HOTAIR may serve as glioma grade predictor and prognostic biomarker. The objective of this timely review is not only to outline the multifaceted pathogenic roles of HOTAIR in the development and pathophysiology of gliomas and brain cancers, but also to delineate the research findings implicating it as a critical regulator of overall brain pathophysiology. While the major focus is on neuro-oncology, wherein HOTAIR represents a particularly potent underlying pathogenic player and a suitable therapeutic target, mechanisms underlying the regulatory actions of HOTAIR in neurodegeneration, traumatic, hypoxic and ischemic brain injuries, and neuropsychiatric disorders are also presented. HOTAIR-mediated epigenetic DNA regulation and molecular sponging of target miRNAs. While the 5′ end of HOTAIR regulates the H3K27 trimethylation activity of the catalytic subunit enhancer of Zeste homolog 2 (EZH2) of the polycomb repressive complex 2 (PRC2), its 3′ end modulates the H3K4 demethylation activity of lysine-specific demethylase 1 (LSD1). HOTAIR also binds to and competitively inhibits the functions of target miRNAs, altering the expression of downstream genes. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is a challenging tumor to treat with radiotherapy, often exhibiting resistance to this treatment modality. To explore the factors influencing radioresistance, we focused on the role of hypoxia‐induced factor‐1α (HIF‐1α), and its interaction with the long noncoding RNA long intergenic nonprotein coding RNA 1116 (LINC01116). We analyzed the LINC01116 expression in EC and EC cell lines/human normal esophageal epithelial cell line (Het‐1A). LINC01116 was silenced/overexpressed in EC109/KYSE30 cells under hypoxia, followed by radioresistance assessment. We measured HIF‐1α levels in hypoxic EC cells and further validated the binding of HIF‐1α with LINC01116, analyzing their interaction in EC cells. We then performed experiments in EC109 cells by transfection them with sh‐HIF‐1α/oe‐LINC01116 to verify the effects. Additonally, we analyzed the localization of LINC01116 and its binding with miR‐3612, followed by a combined experiment performed to validate the results. Our findings indicated that LINC01116 was highly expressed in EC and further elevated in hypoxic EC cells. LINC01116 was expressed at a high level in EC, which was further elevated in EC cells under hypoxic conditions. Knockdown of LINC01116 triggered EC cell apoptosis, thus suppressing radioresistance. Further investigation revealed that HIF‐1α transcriptionally activated LINC01116 expression under hypoxia, and silencing HIF‐1α lowered EC cell radioresistance by downregulating LINC01116. Under hypoxic conditions, LINC01116 could function as a sponge for miR‐3612 and inhibit its expression. This interaction between LINC01116 and miR‐3612 played a crucial role in mediating radioresistance in EC cells. Briefly, under hypoxic conditions, HIF‐1α facilitates radioresistance of EC cells by transcriptionally activating LINC01116 expression and downregulating miR‐3612. [ABSTRACT FROM AUTHOR]

Behavioural differences among social groups can arise from differing ecological conditions, genetic predispositions and/or social learning. In the past, social learning has typically been inferred as responsible for the spread of behaviour by the exclusion of ecological and genetic factors. This 'method of exclusion' was used to infer that 'sponging', a foraging behaviour involving tool use in the bottlenose dolphin (Tursiops aduncus) population in Shark Bay, Western Australia, was socially transmitted. However, previous studies were limited in that they never fully accounted for alternative factors, and that social learning, ecology and genetics are not mutually exclusive in causing behavioural variation. Here, we quantified the importance of social learning on the diffusion of sponging, for the first time explicitly accounting for ecological and genetic factors, using a multi-network version of 'network-based diffusion analysis'. Our results provide compelling support for previous findings that sponging is vertically socially transmitted from mother to (primarily female) offspring. This research illustrates the utility of social network analysis in elucidating the explanatory mechanisms behind the transmission of behaviour in wild animal populations.

Aging affects lipid metabolism and can cause obesity as it is closely related to the disorder of many lipogenic regulatory factors. LncRNAs have been recognized as pivotal regulators across diverse biological processes, but their effects on lipogenesis in aging remain to be further studied. In this work, using RNA sequencing (RNA-Seq), we found that the expression of lncRNA AI504432 was significantly upregulated in the eWAT (epididymal white adipose tissue) of aging mice, and the knockdown of AI504432 notably reduced the expression of several adipogenic genes (e.g., Cebp/α, Srebp-1c, Fasn, Acaca, and Scd1) in senescent adipocytes. The bioinformatics investigation revealed that AI504432 possessed a binding site for miR-1a-3p, and the discovery was verified by the luciferase reporter assay. The expression of Fasn was increased upon the inhibition of miR-1a-3p but restored upon the simultaneous silencing of AI504432. Taken together, our results suggested that AI504432 controlled lipogenesis through the miR-1a-3p/ Fasn signaling pathway. The findings may inspire new therapeutic approaches to target imbalanced lipid homeostasis due to aging. [Display omitted] • Lipogenesis is significantly increased in aging mice and senescent adipocytes. • LncRNA AI504432 promotes lipid synthesis both in vivo and in vitro. • miR-1a-3p is a downstream target of lncRNA AI504432. • LncRNA AI504432 mediates Lipogenesis via the miR-1a-3p/FASN pathway. [ABSTRACT FROM AUTHOR]

In this paper, LINC00839 expression in gastric cancer (GC) was confirmed by real-time quantitative PCR. The function of LINC00839 in GC was detected by loss of function assays. Luciferase assays was performed to confirm the interaction between LINC00839 and miR-1236-3p. Then we investigated the regulatory effect of LINC00839 on miR-1236-3p. The results confirmed that the expression level of LINC00839 in GC was significantly up-regulated. LINC00839 could promote GC cell proliferation, mobility, and invasion. The detection of luciferase reporter gene confirmed that LINC000839 could bind to the binding site of miR-1236-3p. Our findings suggest that LINC00839 promotes GC progression through sponging miR-1236-3p. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear. Methods qRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18. Results circTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression. Conclusion Our data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.

Numerous studies reveal that circular RNAs (circRNAs) affect cancer progression. CircWHSC1 is a novel circRNA that accelerates ovarian cancer progression. Nevertheless, the function of circWHSC1 in regulating breast cancer (BC) is elusive. Here, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to detect the profiles of circWHSC1 and miR-195-5p in BC tissues and corresponding non-tumor tissues. Gain- and loss-of-function assays were implemented both in vivo and ex vivo to verify the significance of circWHSC1 in BC development. BC cell proliferation was estimated by the cell counting kit-8 (CCK-8) and BrdU assays. Transwell assay was implemented to test BC cell migration and invasion. The protein levels of FASN, AMPK and mTOR were determined by Western blot. Moreover, immunohistochemistry was performed to examine Ki67 and FASN expression. As shown by the result, circWHSC1 was up-regulated in BC tissues versus adjacent non-tumor tissues. circWHSC1 overexpression was correlated with higher tumor stages, lymphatic metastasis and worse survival of BC patients. Functionally, overexpressing circWHSC1 amplified proliferation, migration and invasion of BC cell lines and boosted xenograft tumor growth in nude mice. Bioinformatics uncovered that circWHSC1 functioned as a competitive endogenous RNA by sponging miR-195-5p, which was further corroborated by the dual-luciferase reporter assay and RNA immunoprecipitation. miR-195-5p delayed BC progression, which was dampened by circWHSC1 up-regulation. Fatty acid synthase (FASN) was affirmed as a direct target of miR-195-5p. miR-195-5p overexpression curbed FASN expression and activated its downstream AMPK pathway. Inhibition of FASN or activation of the AMPK pathway reversed circWHSC1-mediated oncogenic effects. Collectively, CircWHSC1 acted as an oncogene to expedite BC evolvement by modulating the miR-195-5p/FASN/AMPK/mTOR pathway. [ABSTRACT FROM AUTHOR]

Numerous studies reveal that circular RNAs (circRNAs) affect cancer progression. CircWHSC1 is a novel circRNA that accelerates ovarian cancer progression. Nevertheless, the function of circWHSC1 in regulating breast cancer (BC) is elusive. Here, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to detect the profiles of circWHSC1 and miR-195-5p in BC tissues and corresponding non-tumor tissues. Gain- and loss-of-function assays were implemented both in vivo and ex vivo to verify the significance of circWHSC1 in BC development. BC cell proliferation was estimated by the cell counting kit-8 (CCK-8) and BrdU assays. Transwell assay was implemented to test BC cell migration and invasion. The protein levels of FASN, AMPK and mTOR were determined by Western blot. Moreover, immunohistochemistry was performed to examine Ki67 and FASN expression. As shown by the result, circWHSC1 was up-regulated in BC tissues versus adjacent non-tumor tissues. circWHSC1 overexpression was correlated with higher tumor stages, lymphatic metastasis and worse survival of BC patients. Functionally, overexpressing circWHSC1 amplified proliferation, migration and invasion of BC cell lines and boosted xenograft tumor growth in nude mice. Bioinformatics uncovered that circWHSC1 functioned as a competitive endogenous RNA by sponging miR-195-5p, which was further corroborated by the dual-luciferase reporter assay and RNA immunoprecipitation. miR-195-5p delayed BC progression, which was dampened by circWHSC1 up-regulation. Fatty acid synthase (FASN) was affirmed as a direct target of miR-195-5p. miR-195-5p overexpression curbed FASN expression and activated its downstream AMPK pathway. Inhibition of FASN or activation of the AMPK pathway reversed circWHSC1-mediated oncogenic effects. Collectively, CircWHSC1 acted as an oncogene to expedite BC evolvement by modulating the miR-195-5p/FASN/AMPK/mTOR pathway.

Therapeutic effectiveness in breast cancer can be limited by the underlying mechanisms of pathogenesis, including epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and drug resistance. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are master regulators of gene expression and are functionally important mediators in these mechanisms of pathogenesis. Intricate crosstalks between these non-coding RNAs form complex regulatory networks of post-transcriptional gene regulation. Depending on the specific lncRNA/miRNA interaction, the lncRNA-miRNA axis can have tumor suppressor or oncogenic effects, thus defining the lncRNA-miRNA axis is important for determining targetability. Herein, we summarize the current literature describing lncRNA-miRNA interactions that are critical in the molecular mechanisms that regulate EMT, CSCs and drug resistance in breast cancer. Further, we review both the well-studied and potential novel mechanisms of lncRNA-miRNA interactions in breast cancer. [ABSTRACT FROM AUTHOR]

Recent studies have shown that circular RNAs (circRNAs) are involved in many human diseases, but their roles in secondary damage after spinal cord injury (SCI) remain unclear. In the current study circRNA sequencing was performed in the damaged tissues of SCI rats on the seventh day after injury, and related molecular mechanisms were investigated. Quantitative PCR validations of molecules that exhibited significantly altered expression in SCI mice were performed. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to assess differentially expressed circRNAs. A novel circRNA‐2960 was the most significantly upregulated in the SCI group. It could downregulate its target molecule miRNA‐124, then exacerbate the inflammatory response and induce apoptosis at the lesion site. Disrupting circRNA‐2960 expression promoted recovery of tissues affected by secondary SCI damage. The results of the present study may provide new insight into the mechanisms of secondary injury in SCI, and a new molecular marker for the diagnosis and treatment of SCI. [ABSTRACT FROM AUTHOR]

Behavioural time budgets of organisms reflect their reaction norms to environmental conditions and, as such, indicate their behavioural plasticity. In environments which limit the activity time of organisms, efficient organization of behaviours is critical to enhancing performance to achieve necessary functions and minimize time and/or energetic costs. We investigated variations in behavioural time budgets of a common deposit-feeding crab, Scopimera intermedia, to the spatio-temporal scales of environmental changes experienced on sandy shores in the monsoonal tropics, where activity times are restricted by the tides. Activity levels of the crabs varied strongly with air temperature, with crabs emerging from the sediments only when air temperature exceeded ~ 20 °C. Behavioural water uptake increased in frequency with both feeding rate and environmental temperature, and was often followed by waving displays. Water uptake and waving, therefore, appear to be multifunctional behaviours, as not only do the crabs replenish water for feeding and wave their chelipeds to court females, but these behaviours can also contribute to thermoregulation, enhancing cooling when taking up water from the sediment surface. Such plastic and multifunctional behavioural traits are likely a widespread solution for survival and reproductive success in harsh and dynamic environments, where specialized traits are energetically costly and time-inefficient to optimize performance. Significance statement: Surviving in extreme and variable environments is challenging due to the potentially substantial energetic cost animals need to undertake in order to maximize performances under contrasting conditions. This study reveals a multitasking strategy adopted by the sand-bubbler crab to survive hot and variable temperatures within a limited activity time on tropical sandy shores. Behaviours of the crabs are strongly temperature dependent; and when active whilst the tide is out the crabs flexibly adjust their activity times to feed, stay cool and attract mates using a limited set of multifunctional behaviours. Specialized traits are therefore not necessary to achieve these critical functions and, as such, this study highlights the importance of this plastic, multitasking strategy as a common solution for animals to endure highly variable environments with minimal cost. [ABSTRACT FROM AUTHOR]

Abstract Background Small nucleolar RNA host gene 6 (SNHG6) regulates diverse biological processes in cancers. Potential function of SNHG6 in human colon and rectal adenocarcinoma (CRC) was evaluated. Methods Quantitative real-time polymerase chain reaction, MTT assays, Colony formation assays, Transwell assay, Western Blotting and Luciferase reporter assays were performed to measure the biological functions and potential molecular mechanisms of SNHG6 in CRC. Results SNHG6 was over-expressed in CRC, and high expression of s SNHG6 were associated with short survival times. We then identified miR-101-3p as an inhibitory target of SNHG6. Knockdown of SNHG6 significantly decreased miR-101-3p expression. Moreover, silenced SNHG6 obviously inhibited CRC cell growth, weakened cell invasion capacity and blocked the Wnt/β-catenin signaling pathway. Conclusion SNHG6 could regulate the progression of CRC via modulating the expression levels of miR-101-3p and the activity of Wnt/β-catenin signaling.

Background: Hepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear. Methods: qRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18. Results: circTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression. Conclusion: Our data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment. [ABSTRACT FROM AUTHOR]

Purpose: Circular RNAs (circRNAs) constitute a class of regulatory RNAs that are thought to play important roles in tumor initiation and progression. Several studies have reported that circRNAs may be involved in various biological processes via networks of competing endogenous RNAs (ceRNAs). However, the regulatory roles and underlying mechanisms of circRNAs in cervical cancer (CC) still largely remain to be resolved. Methods: CircNFATC3 (hsa_circ_0005615) expression was assessed in CC cell lines (SiHa, H8) using circRNA microarray analysis, whereas qRT-PCR was used to detect circNFATC3 and miR-9-5p expression in primary human CC tissues and cell lines. The tumor promoting role of circNFATC3 was verified in CC cells using a series of functional assays, and interactions between circNFATC3, miR-9-5p and syndecan-2 (SDC2) were investigated using dual-luciferase reporter assays. SDC2 protein expression was detected using Western blotting and immunohistochemistry. The tumor promoting role of circNFATC3 was confirmed in vivo using a CC xenograft model. Results: We found that circNFATC3 expression was upregulated in primary CC tissues and positively correlated with CC tumor size and stromal invasion. In addition, we found that exogenous circNFATC3 overexpression enhanced the proliferation, migration and invasion of HeLa cells, while its knockdown reduced the malignancy of SiHa cells. We also found that circNFATC3 may act directly as a miR-9-5p sponge to regulate SDC2 expression and its downstream signaling pathways, thereby enhancing CC development. Conclusion: Our data indicate that circNFATC3 sponges miR-9-5p to regulate SDC2 expression and, thereby, to promote CC tumor development. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer.

The slag adjustment during steel smelting in arc steelmaking furnaces, the conditions for sponging and the gas load at different amounts of supplied oxygen and the various contents of carbon in the melt were considered. The amount of blown carbon-containing materials in the steelmaking bath is determined.

Endometriosis is a chronic gynecological disorder affecting the quality of life and fertility of many women around the world. Heterogeneous and non-specific symptoms may lead to a delay in diagnosis, with treatment options limited to surgery and hormonal therapy. Hence, there is a need to better understand the pathogenesis of the disease to improve diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation but remain relatively under investigated in endometriosis. Mutational and transcriptomic studies have implicated lncRNAs in the pathogenesis of endometriosis. Single-nucleotide polymorphisms (SNPs) in lncRNAs or their regulatory regions have been associated with endometriosis. Genome-wide transcriptomic studies have identified lncRNAs that show deregulated expression in endometriosis, some of which have been subjected to further experiments, which support a role in endometriosis. Mechanistic studies indicate that lncRNAs may regulate genes involved in endometriosis by acting as a molecular sponge for miRNAs, by directly targeting regulatory elements via interactions with chromatin or transcription factors or by affecting signaling pathways. Future studies should concentrate on determining the role of uncharacterized lncRNAs revealed by endometriosis transcriptome studies and the relevance of lncRNAs implicated in the disease by in vitro and animal model studies.

Long noncoding RNA maternally expressed gene 3 (lncRNA‐MEG3) is an important regulator in multiple biological functions. However, lncRNA‐MEG3's function in cattle growth and regulatory mechanism on bovine skeletal muscle development has not yet been well studied. In this project, we first investigated lncRNA‐MEG3's expression profile and detected that it was highly expressed in bovine skeletal muscle tissue and its RNA level was kept increasingly during the early phase of bovine primary myoblast differentiation. Using luciferase reporter assays, we identified the lncRNA‐MEG3 core promoter containing putative transcription factor binding site for myocyte enhancer factor 2C (MEF2C). Interestingly, we found that LncRNA‐MEG3 could significantly upregulate and downregulate myosin heavy chain (MHC), myogenin (MyoG), and MEF2C through overexpression and RNAi strategies, respectively. Using luciferase reporter assays, we also verified lncRNA‐MEG3 as a miR‐135 sponge. Overexpression of miR‐135 markedly inhibited the wild type of lncRNA‐MEG3, but not the mutant lncRNA‐MEG3 reporter. The luciferase activity of miR‐135 sensor could be rescued by lncRNA‐MEG3 via competing for miRNA‐135. In addition, the luciferase activity of MEF2C was significantly upregulated by the wild type of lncRNA‐MEG3. This study, for the first time, revealed that lncRNA‐MEG3 could promote bovine skeletal muscle differentiation via interacting with miRNA‐135 and MEF2C. The results were valuable for further studies and applications of lncRNA related roles in beef molecular breeding. [ABSTRACT FROM AUTHOR]

Understanding the exact pathogenesis of cancer is difficult due to heterogenous nature of tumor cells and multiple factors that cause its initiation and development. Treatment of cancer is mainly based on surgical resection, chemotherapy, radiotherapy and their combination, while gene therapy has been emerged as a new kind of therapy for cancer. Post-transcriptional regulation of genes has been of interest in recent years and among various types of epigenetic factors that can modulate gene expression, short non-coding RNAs known as microRNAs (miRNAs) have obtained much attention. The stability of mRNA decreases by miRNAs to repress gene expression. miRNAs can regulate tumor malignancy and biological behavior of cancer cells and understanding their function in tumorigenesis can pave the way towards developing new therapeutics in future. One of the new emerging miRNAs in cancer therapy is miR-218 that increasing evidence highlights its anti-cancer activity, while a few studies demonstrate its oncogenic function. The miR-218 transfection is promising in reducing progression of tumor cells. miR-218 shows interactions with molecular mechanisms including apoptosis, autophagy, glycolysis and EMT, and the interaction is different. miR-218 induces apoptosis, while it suppresses glycolysis, cytoprotective autophagy and EMT. Low expression of miR-218 can result in development of chemoresistance and radio-resistance in tumor cells and direct targeting of miR-218 as a key player is promising in cancer therapy. LncRNAs and circRNAs are nonprotein coding transcripts that can regulate miR-218 expression in human cancers. Moreover, low expression level of miR-218 can be observed in human cancers such as brain, gastrointestinal and urological cancers that mediate poor prognosis and low survival rate. [Display omitted] • The epigenetic dysregulation in human cancers. • The abnormal expression of miR-218 facilitates carcinogenesis. • miR-218 controls growth, metastasis and cell cycle arrest. • The radioresistance and chemoresistance can be modulated by miR-218. • LncRNAs and circRNAs sponge miR-218. [ABSTRACT FROM AUTHOR]

Background and Objective: Esophageal cancer is one of the most common malignant digestive tract tumors. Despite various treatment methods, the prognosis of patients remains unsatisfactory, largely due to an insufficient understanding of the mechanisms involved in the pathogenesis and progression of esophageal cancer. More than 98% of the nucleotide sequences in the human genome do not encode proteins, and their transcription products are noncoding RNAs (ncRNAs), mainly long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Experiments have shown that lncRNAs and miRNAs play crucial roles in the occurrence and progression of various human malignancies. These ncRNAs influence the progression of esophageal cancer through an intricate regulatory network. We herein summarized the roles and mechanisms of the lncRNA-miRNA axis in esophageal cancer cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), invasion and metastasis, drug resistance, radiotherapy resistance, and angiogenesis. This review provides a rationale for anticancer therapy that targets the lncRNA-miRNA axis in esophageal cancer., Methods: Related articles published in the PubMed database between 05/30/2008 to 09/10/2022 were identified using the following terms: "lncRNA AND miRNA AND esophageal cancer", "lncRNA AND miRNA AND cell proliferation", "lncRNA AND miRNA AND apoptosis", "lncRNA AND miRNA AND EMT", "lncRNA AND miRNA AND invasion and metastasis", "lncRNA AND miRNA AND drug resistance", and "lncRNA AND miRNA AND radiotherapy resistance". Published articles written in English available to readers were considered., Key Content and Findings: We summarized the roles of the lncRNA-miRNA axis in the progression of esophageal cancer, including cell proliferation, apoptosis, EMT, invasion and metastasis, drug resistance, radio resistance, and other progressions, and determined that the lncRNA-miRNA axis may serve as a potential clinical treatment target for esophageal cancer., Conclusions: The lncRNA-miRNA axis is closely related to the progression of esophageal cancer and may act as a potential biological target for the clinical treatment of patients with esophageal cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1449/coif). ZW reports funding support from the National Natural Science Foundation of China (grant No. 81872371). SZ reports funding support from the Nature and Science Fund of Key Cultivate Program from Wannan Medical College, China (grant No. WK2018ZF06), the Talent Scientific Research Start-Up Foundation of Yijishan Hospital, Wannan Medical College (grant No. YR201806), and the Science Fund for Key Program of Three Creative Research of Yijishan Hospital of Wannan Medical College (grant No. Z1810). The other author has no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

In this paper, LINC00839 expression in gastric cancer (GC) was confirmed by real-time quantitative PCR. The function of LINC00839 in GC was detected by loss of function assays. Luciferase assays was performed to confirm the interaction between LINC00839 and miR-1236-3p. Then we investigated the regulatory effect of LINC00839 on miR-1236-3p. The results confirmed that the expression level of LINC00839 in GC was significantly up-regulated. LINC00839 could promote GC cell proliferation, mobility, and invasion. The detection of luciferase reporter gene confirmed that LINC000839 could bind to the binding site of miR-1236-3p. Our findings suggest that LINC00839 promotes GC progression through sponging miR-1236-3p. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer. [ABSTRACT FROM AUTHOR]

An apparently vertically, socially transmitted foraging specialization (‘sponging’) in bottlenose dolphins (Tursiops sp.) is observed in two adjacent gulfs within Shark Bay, Western Australia, where sponging has possibly spread from independent innovations. We designed an individual-based model based on empirical data, to investigate the conditions (of learning fidelity and fitness benefits for spongers) under which sponging could be established and maintained. Simulations show that sponging is unlikely to be established from a single innovation event but the probability increases with independent innovation events. Once established, however, it can be maintained in the absence of fitness benefits for spongers, if learning fidelity of daughters is virtually 100%. Smaller learning fidelities can be compensated for with fitness benefits for spongers, but these benefits must be 5% and 10%, respectively, to compensate for learning fidelities of 96.25% and 92%. Furthermore, we estimated the time since the emergence of sponging by tracking the average pairwise relatedness among spongers over time and comparing it to empirical estimates. For the eastern gulf of Shark Bay, we show that sponging might have been in place for at least 120 years if it originated from a single innovation event. For comparison of vertical, social transmission to other trait acquisition methods, we ran simulations in which sponging was either a genetic trait or acquired solely by innovation. In these simulations, sponging could be maintained but the simulation results and empirical data did not match. Hence vertical social transmission is a more feasible mechanism to explain the spread of sponging. [Copyright &y& Elsevier]

Endometriosis is a chronic gynecological disorder affecting the quality of life and fertility of many women around the world. Heterogeneous and non-specific symptoms may lead to a delay in diagnosis, with treatment options limited to surgery and hormonal therapy. Hence, there is a need to better understand the pathogenesis of the disease to improve diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation but remain relatively under investigated in endometriosis. Mutational and transcriptomic studies have implicated lncRNAs in the pathogenesis of endometriosis. Single-nucleotide polymorphisms (SNPs) in lncRNAs or their regulatory regions have been associated with endometriosis. Genome-wide transcriptomic studies have identified lncRNAs that show deregulated expression in endometriosis, some of which have been subjected to further experiments, which support a role in endometriosis. Mechanistic studies indicate that lncRNAs may regulate genes involved in endometriosis by acting as a molecular sponge for miRNAs, by directly targeting regulatory elements via interactions with chromatin or transcription factors or by affecting signaling pathways. Future studies should concentrate on determining the role of uncharacterized lncRNAs revealed by endometriosis transcriptome studies and the relevance of lncRNAs implicated in the disease by in vitro and animal model studies. [ABSTRACT FROM AUTHOR]

Russia behaves in a fundamentally different way. The authors compare Russia's international behavior with the clinical diagnoses of Borderline Personality Disorder. They describe various traits of this disorder with an emphasis on handling those suffering from it. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been identified to be involved in a variety of human diseases such as cancers, cardiovascular diseases, and autoimmune diseases. In recent years, the role of circRNAs in the development of kidney diseases in nephrology has been gradually recognized., Objective: We updated and described the current status of circRNAs in kidney diseases in nephrology. We particularly focused on the roles and mechanisms of circRNAs in systemic lupus erythematosus and lupus nephritis., Methods: We summarized recent reports published on PubMed, Web of Science, Scopus, Scielo databases using keywords circRNAs, kidney diseases or renal diseases, or systemic lupus erythematosus., Results: Studies of circRNAs in certain kidney diseases, such as acute kidney injury, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, IgA nephropathy, diabetic nephropathy, hypertensive renal damage, and particular lupus nephritis address the function and pathogenesis of circRNAs. Mechanisms of circRNAs in the above human kidney diseases so far have focused on the role of sponging microRNAs and regulating the expression of target genes. Moreover, circRNAs have been detected in blood, urine, and kidney tissue samples. These results suggest that circRNAs can serve as biomarkers for the diagnosis and monitoring of the progression of kidney diseases., Conclusion: CircRNAs play important roles in the pathogenesis, diagnosis, and treatment of kidney diseases emphasizing lupus nephritis in nephrology., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Androgenetic alopecia (AGA) is an androgen-dependent polygenic hereditary disease., Methods: Diseased hair follicles from 5 AGA patients and normal hair follicles from 5 healthy individuals were selected as specimens to carry out whole transcriptome sequencing. Multiple high-expression circular RNAs (circRNAs) were screened from the diseased group. We further verified the presence of the circRNAs in the clinical specimens by real-time fluorescence quantitative PCR (qRT-PCR)., Results: In total, 100 circRNAs were significantly upregulated, and 184 circRNAs were significantly downregulated. The top 10 upregulated circRNAs were hsa_circ_0101041, hsa_circ_0001578, hsa_circ_0135062, hsa_circ_0002980, hsa_circ_0005062, hsa_circ_0072688, hsa_circ_0133954, hsa_circ_0001079, hsa_circ_0005974, hsa_circ_0000489. The top 10 downregulated circRNAs were hsa_circ_0001278, hsa_circ_0031482, hsa_circ_0008285, hsa_circ_0003784, hsa_circ_0077096, hsa_circ_0001148, hsa_circ_0006886, hsa_circ_0000638, hsa_circ_0084521, and hsa_circ_0101074. Among top 10 upregulated circRNAs, hsa_circ_0001079 showed significantly high expression via large-sample verification and clinical application potential. Based on a database comparison and base pairing analysis, we found that has-miR-136-5p bound to hsa_circ_0001079 and that hsa-miR-136-5p had potential binding sites with Wnt5A., Conclusion: In summary, through high-throughput sequencing and bioinformatic analysis, a potential diagnostic marker for alopecia and a key circRNA that might adsorb microRNA (miRNA) through a sponging mechanism, thus mediating alopecia, were discovered in this study., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

A lariat cap is a naturally occurring substitute of a conventional mRNA cap and is found in a particular genomic setting in a few eukaryotic microorganisms. It is installed by the lariat capping ribozyme acting in cis. In principle, any RNA molecule in any organism can be equipped with a lariat cap in vivo when expressed downstream of a lariat capping ribozyme. Lariat capping is thus a versatile tool for studying the importance of the 5' end structure of RNA molecules. In this chapter, we present protocols to validate the presence of the lariat cap and measure the efficiency of in vivo cleavage by the lariat capping ribozyme.

Objective: Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies and the fifth most common cancer in women. Circular RNAs (circRNAs) have been shown to play vital functions in cancers, but few studies have focused on the functions and mechanism of dysregulated circRNAs in PTC., Methods: Quantitative reverse transcription PCR was used to measure circ-NCOR2 levels in PTC tissues and cell lines. The functions of circ-NCOR2 in PTC were examined by analysis using the cell counting kit-8, clone forming, flow cytometry, and Transwell experiments. Bioinformatic analysis and dual luciferase reporter gene testing were used to identify the mechanisms of circ-NCOR2., Results: Circ-NCOR2 overexpression was observed in PTC tissues and cells. Silenced or overexpressed expression of circ-NCOR2 strikingly attenuated or facilitated, respectively, the growth, migration, and invasion of PTC cells. Mechanistically, miR-615a-5p was identified as the target of circ-NCOR2. Moreover, circ-NCOR2 enhanced the expression of metastasis-associated protein 2 (MTA2) by sponging miR-615a-5p, thereby facilitating PTC cell progression., Conclusions: Taken together, our findings reveal a novel circ-NCOR2/miR-615a-5p/MTA2 axis in PTC, which could become a potential therapeutic target for this disease.

The circular RNA RAPGEF5 (circRAPGEF5) is generated from five exons of the RAPGEF5 gene and abnormal expression in papillary thyroid cancer (PTC). However, whether circRAPGEF5 plays a role in PTC tumorigenesis remains unclear. The aim of the present study was to investigate the role of circRAPGEF5 in PTC. The results showed that circRAPGEF5 was upregulated in PTC tissues and cell lines. circRAPGEF5 knockdown inhibited cell proliferation, migration, and invasion in vitro; and circRAPGEF5 silencing downregulated fibroblast growth factor receptor 1 (FGFR1) expression by "sponging" miR-198, suppressing the aggressive biological behaviors of PTC. Luciferase reporter assays confirmed that circRAPGEF5 interacted with miR-198 and that miR-198 interacted with the 3' UTR of FGFR1 to downregulate its expression. Xenograft experiments confirmed that circRAPGEF5 knockdown suppressed FGFR1-mediated tumor growth by promoting miR-198 expression. circRAPGEF5 acts as a tumor promoter via a novel circRAPGEF5/miR-198/FGFR1 axis, providing a potential biomarker and therapeutic target for the management of PTC., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Non-coding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting, e.g., the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.