Nucleic acids have the potential to form not only duplexes, but also various non-canonical secondary structures in living cells. Non-canonical structures play regulatory functions mainly in the central dogma. Therefore, nucleic acid targeting molecules are potential novel therapeutic drugs that can target 'undruggable' proteins in various diseases. One of the concerns of small molecules targeting nucleic acids is selectivity, because nucleic acids have only four different building blocks. Three- and four-stranded non-canonical structures, triplexes and quadruplexes, respectively, are promising targets of small molecules because their three-dimensional structures are significantly different from the canonical duplexes, which are the most abundant in cells. Here, we describe some basic properties of the triplexes and quadruplexes and small molecules targeting the triplexes and tetraplexes.

Ovarian cancer remains one of the deadliest gynecological malignancies, with a persistently high mortality rate despite promising advancements in immunotherapy. Aberrant splicing events play a crucial role in cancer heterogeneity and treatment resistance. Many splicing variants, especially those involving key molecular markers such as BRCA1/2, are closely linked to disease progression and treatment outcomes. These variants and related splicing factors hold significant clinical value as diagnostic and prognostic biomarkers and therapeutic targets. This review provides a comprehensive overview of splicing variants in ovarian cancer, emphasizing their role in metastasis and resistance, and offers insights to advance biomarker development and treatment strategies.

The small nucleolar RNA (snoRNA) SNORD116 is a small non-coding RNA of interest across multiple biomedical fields of research. Much of the investigation into SNORD116 has been undertaken in the context of the congenital disease Prader-Willi syndrome, wherein SNORD116 expression is lost. However, emerging evidence indicates wider roles in various disease and tissue contexts such as cellular growth, metabolism and signalling. Nevertheless, a conclusive mechanism of action for SNORD116 remains to be established. Here, we review the key findings from these investigations, with the aim of identifying common elements from which to elucidate potential targets and mechanisms of SNORD116. A key recurring element identified is disruption to the insulin/IGF-1 and PI3K/mTOR signalling pathways, contributing to many of the phenotypes associated with SNORD116 modulation explored in this review.

Dynamic DNA nanodevices, known for their high programmability and controllability, are pivotal in intracellular biomarker imaging. However, these nanodevices often suffer from inadequate detection sensitivity and specificity due to limited cellular loading capacity and low signal feedback. Herein, we engineered an integrated multi-site recognition and multi-signal output of four-leaf clover dynamic DNA nanodevice (MEMORY) that enables sensitive and accurate intracellular long noncoding RNA (lncRNA) imaging. MEMORY features one fluorophore (FAM)-modified cross-shaped structure as spatial-confinement scaffolds loaded with four identical quenchers (BHQ1)-modified recognition probes (RPs), ensuring a low background signal initially. In the presence of target lncRNA, the multiple recognition sites of MEMORY facilitate hybridization with the target to selectively release the RPs, exposing the toehold region and outputting the green fluorescence (FAM) signal. Furthermore, the exposed toehold region can trigger efficient and rapid hybridization chain reaction (HCR) amplification, outputting the red fluorescence (Cy5) signal. MEMORY's multiple recognition sites increase the likelihood of target collisions, enhancing reaction efficiency, while its multi-signal output provides sequential feedback through FAM and Cy5, boosting overall signal intensity. With the lncRNA metastasis-related lung adenocarcinoma transcript 1 (MALAT1) as a detection model, MEMORY offers a linear detection range from 1 pM to 100 nM, with a limit of detection of 0.29 pM. We demonstrated that MEMORY can differentiate between normal and tumor cells based on intracellular MALAT1 imaging. This integrated DNA nanodevice will offer valuable tools for sensitive and accurate imaging of intracellular biomarkers.

Despite critical roles in diseases, human pathways acting on strictly nuclear non-coding RNAs have been refractory to forward genetics. To enable their forward genetic discovery, we developed a single-cell approach that "Mirrors" activities of nuclear pathways with cytoplasmic fluorescence. Application of Mirror to two nuclear pathways targeting MALAT1's 3' end, the pathway of its maturation and the other, the degradation pathway blocked by the triple-helical Element for Nuclear Expression (ENE), identified nearly all components of three complexes: Ribonuclease P and the RNA Exosome, including nuclear DIS3, EXOSC10, and C1D, as well as the Nuclear Exosome Targeting (NEXT) complex. Additionally, Mirror identified DEAD-box helicase DDX59 associated with the genetic disorder Oral-Facial-Digital syndrome (OFD), yet lacking known substrates or roles in nuclear RNA degradation. Knockout of DDX59 exhibits stabilization of the full-length MALAT1 with a stability-compromised ENE and increases levels of 3'-extended forms of small nuclear RNAs. It also exhibits extensive retention of minor introns, including in OFD-associated genes, suggesting a mechanism for DDX59 association with OFD. Mirror efficiently identifies pathways acting on strictly nuclear non-coding RNAs, including essential and indirectly-acting components, and, as a result, uncovers unexpected links to human disease.

Meis1 is a transcription factor involved in numerous functions including development and proliferation and has been previously shown to harness cell cycle progression. In this study, we used in silico analysis to predict that miR-499-5p targets Meis1 and that Malat1 sponges miR-499-5p. For the first time, we demonstrated that the overexpression of miR-499-5p led to the downregulation of Meis1 mRNA and protein in C166 cells by directly binding to its 3'UTR. Moreover, knocking down Malat1 increased miR-499-5p expression, subsequently suppressing Meis1. Through BrdU incorporation assay, we showed that the knockdown of Malat1, Meis1, or mimicking with miR-499-5p promoted cell proliferation. Enrichment analyses on proteins identified via mass spectrometry after manipulating Malat1, miR-499-5p, or Meis1 revealed a multitude of differentially expressed proteins related to cell cycle, cell division, and key pathways like Wnt and mTOR, essential for cell proliferation. Collectively, our findings confirm that Malat1 sponges miR-499-5p, regulating Meis1, and that Malat1/miR-499-5p/Meis1 could potentially form an axis that has a pivotal influence on cellular proliferation.

Exosomal non-coding RNAs (ncRNAs) have become essential contributors to advancing and treating lung cancers (LCs). The development of liquid biopsies that utilize exosomal ncRNAs (exo-ncRNAs) offers an encouraging method for diagnosing, predicting, and treating LC. This thorough overview examines the dual function of exo-ncRNAs as both indicators for early diagnosis and avenues for LC treatment. Exosomes are tiny vesicles secreted by various cells, including cancerous cells, enabling connection between cells by delivering ncRNAs. These ncRNAs, which encompass circular RNAs, long ncRNAs, and microRNAs, participate in the modulation of gene expression and cellular functions. In LC, certain exo-ncRNAs are linked to tumour advancement, spread, and treatment resistance, positioning them as promising non-invasive indicators in liquid biopsies. Additionally, targeting these ncRNAs offers potential for innovative treatment approaches, whether by suppressing harmful ncRNAs or reinstating the activity of tumour-suppressing ones. This review emphasizes recent developments in the extraction and analysis of exo-ncRNAs, their practical applications in LC treatment, and the challenges and prospects for translating these discoveries into clinical usage. Through this detailed examination of the current state of the art, we aim to highlight the significant potential of exo-ncRNAs for LC diagnostics and treatments.

Colorectal cancer (CRC) ranks among the top three cancers globally in both incidence and mortality, posing a significant public health challenge. Most CRC cases are diagnosed at intermediate to advanced stages, and reliable biomarkers for early detection are lacking. Long non-coding RNAs (lncRNAs) have been implicated in various cancers, including CRC, playing key roles in tumor development, progression, and prognosis.

A comprehensive search of the PubMed database was conducted to identify relevant studies on the early diagnosis of CRC. Bioinformatics analysis was performed to explore lncRNA-mRNA networks, leading to the identification of five potential blood biomarkers. Expression analysis was carried out using the GEPIA and GEO online databases, focusing on MYC and STAT3. Differential expression between normal and CRC tissues was assessed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the diagnostic potential of these markers. Quantitative Real-Time PCR (qRT-PCR) was performed to validate MYC and STAT3 expression levels, and findings were further confirmed using the Human Protein Atlas (HPA) database.

Database analysis revealed significant differential expression of MYC and STAT3 between normal and CRC tissues. ROC analysis demonstrated the diagnostic potential of these markers. qRT-PCR validation confirmed the differential expression patterns observed in the databases. Validation through the HPA database further supported these findings, confirming the potential of MYC and STAT3 as diagnostic biomarkers for CRC.

Our results suggest that MYC and STAT3 are promising diagnostic biomarkers for CRC, offering new insights into its pathophysiology and potential for targeted therapies.

RNA conformational diversity has fundamental biological roles1-5, but direct visualization of its full conformational space in solution has not been possible using traditional biophysical techniques. Using solution atomic force microscopy, a deep neural network and statistical analyses, we show that the ribonuclease P (RNase P) RNA adopts heterogeneous conformations consisting of a conformationally invariant core and highly flexible peripheral structural elements that sample a broad conformational space, with amplitudes as large as 20-60 Å in a multitude of directions, with very low net energy cost. Increasing Mg2+ drives compaction and enhances enzymatic activity, probably by narrowing the conformational space. Moreover, analyses of the correlations and anticorrelations between spatial flexibility and sequence conservation suggest that the functional roles of both the structure and dynamics of key regions are embedded in the primary sequence. These findings reveal the structure-dynamics basis for the embodiment of both enzymatic precision and substrate promiscuity in the RNA component of the RNase P. Mapping the conformational space of the RNase P RNA demonstrates a new general approach to studying RNA structure and dynamics.

Oral cancer progresses from asymptomatic to advanced stages, often involving cervical lymph node metastasis, resistance to chemotherapy, and an unfavorable prognosis. Clarifying its potential mechanisms is vital for developing effective theraputic strategies. Recent research suggests a substantial involvement of non-coding RNA (ncRNA) in the initiation and advancement of oral cancer. However, the underlying roles and functions of various ncRNA types in the growth of this malignant tumor remain unclear. Competing endogenous RNAs (ceRNAs) refer to transcripts that can mutually regulate each other at the post-transcriptional level by vying for shared miRNAs. Networks of ceRNAs establish connections between the functions of protein-coding mRNAs and non-coding RNAs, including microRNA, long non-coding RNA, pseudogenic RNA, and circular RNA, piwi-RNA, snoRNA. A growing body of research has indicated that imbalances in ceRNAs networks play a crucial role in various facets of oral cancer, including development, metastasis, migration, invasion, and inflammatory responses. Hence, delving into the regulatory pathways of ceRNAs in oral cancer holds the potential to advance our understanding of the pathological mechanisms, facilitate early diagnosis, and foster targeted drug development for this malignancy. The present review summarized the fundamental role of ceRNA network, discussed the limitations of current ceRNA applications, which have been improved through chemical modification and carrier delivery as new biomarkers for diagnosis and prognosis is expected to offer a groundbreaking therapeutic approach for individuals with oral cancer.

Lung Cancer (LC) is characterized by chemoresistance, which poses a significant clinical challenge and results in a poor prognosis for patients. Long non-coding RNAs (lncRNAs) have recently gained recognition as crucial mediators of chemoresistance in LC. Through the regulation of key cellular processes, these molecules play important roles in the progression of LC and response to therapy. The mechanisms by which lncRNAs affect chemoresistance include the modulation of gene expression, chromatin structure, microRNA interactions, and signaling pathways. Exosomes have emerged as key mediators of lncRNA-driven chemoresistance, facilitating the transfer of resistance-associated lncRNAs between cancer cells and contributing to tumor development. Consequently, exosomal lncRNAs may serve as biomarkers and therapeutic targets for the treatment of LC. Therapeutic strategies targeting lncRNAs offer novel approaches to circumvent chemoresistance. Different approaches, including RNA interference (RNAi) and antisense oligonucleotides (ASOs), are available to degrade lncRNAs or alter their function. ASO-based therapies are effective at reducing lncRNA expression levels, increasing chemotherapy sensitivity, and improving clinical outcomes. The use of these strategies can facilitate the development of targeted interventions designed to disrupt lncRNA-mediated mechanisms of chemoresistance. An important aspect of this review is the discussion of the complex relationship between lncRNAs and drug resistance in LC, particularly through exosomal pathways, and the development of innovative therapeutic strategies to enhance drug efficacy by targeting lncRNAs. The development of new pathways and interventions for treating LC holds promise in overcoming this resistance.

Parkinson's disease (PD) is one of the most prevalent diseases of central nervous system that is caused by degeneration of the substantia nigra's dopamine-producing neurons through apoptosis. Apoptosis is regulated by initiators' and executioners' caspases both in intrinsic and extrinsic pathways, further resulting in neuronal damage. In that context, targeting apoptosis appears as a promising therapeutic approach for treating neurodegenerative diseases. Non-coding RNAs-more especially, microRNAs, or miRNAs-are a promising target for the therapy of neurodegenerative diseases because they are essential for a number of cellular processes, including signaling, apoptosis, cell proliferation, and gene regulation. It is estimated that a substantial portion of coding genes (more than 60%) are regulated by miRNAs. These small regulatory molecules can have wide-reaching consequences on cellular processes like apoptosis, both in terms of intrinsic and extrinsic pathways. Furthermore, it was recommended that a disruption in miRNA expression levels could also result in perturbation of typical apoptosis pathways, which may be a factor in certain diseases like PD. The latest research on miRNAs and their impact on neural cell injury in PD models by regulating the apoptosis pathway is summarized in this review article. Furthermore, the importance of lncRNA/circRNA-miRNA-mRNA network for regulating apoptosis pathways in PD models and treatment is explored. These results can be utilized for developing new strategies in PD treatment.

The p53 is a crucial tumor suppressor and transcription factor that participates in apoptosis and senescence. It can be activated upon DNA damage to regulate the expression of a series of genes. Previous studies have demonstrated that some specific lncRNAs are part of the TP53 regulatory network. To enhance our understanding of the relationship between lncRNAs and P53 in cancers, we review the localization, structure, and function of some lncRNAs that are related to the mechanisms of the p53 pathway or serve as p53 transcriptional targets.

Breast cancer is a significant health challenge for women globally, including the Pakistani population. Numerous pathways and small molecules like noncoding ribonucleotides are implicated in breast cancer development and progression. Among these, lncRNAs, have garnered considerable attention due to their role in breast cancer tumorigenesis and metastasis. In the current study involving 52 mammary tumor samples from the Pakistani population, the expression of lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript 1) was studied via RT-PCR (Real-Time polymerase chain reaction). In addition, PI3K/AKT/mTOR pathway expression was also assessed through RT-PCR and immunohistochemistry in breast cancer patient samples. The study also investigated the cross-talk of lncRNA MALAT1 and PI3K pathway genes by inhibiting it with PI3K inhibitor (LY294002) in MDA-MB-231 cell line. Furthermore, lncRNA MALAT1 was silenced in MDA-MB-231 cells using siRNA to determine its impact on breast cancer proliferation and metastasis. The results revealed an upregulated expression of MALAT1 and PI3K/AKT/mTOR pathway genes in grade II and III breast tissue samples before chemotherapy. The proliferation, growth, and invasion of breast cancer cells were significantly reduced upon MALAT1 silencing in MDA-MB-231. Further, its downregulation substantially reduced the PI3K pathway expression levels at mRNA and protein levels. In conclusion, the current study suggests that MALAT1 could serve as a therapeutic target for breast cancer, underscoring its role in breast cancer proliferation and metastasis. Moreover, the study proposes a mechanism of action of MALAT1, demonstrating that its inhibition can reduce the expression of the PI3K/AKT/mTOR axis. These findings emphasize the potential significance of targeting MALAT1 as a therapeutic strategy for breast cancer, and further exploration of this interaction is warranted to gain deeper insight into the molecular mechanism of this lncRNA.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are two typical types of non-coding RNAs that interact and play important regulatory roles in many animal organisms. Exploring the unknown interactions between lncRNAs and miRNAs contributes to a better understanding of their functional involvement. Currently, studying the interactions between lncRNAs and miRNAs heavily relies on laborious biological experiments. Therefore, it is necessary to design a computational method for predicting lncRNA-miRNA interactions. In this work, we propose a method called MPGK-LMI, which utilizes a graph attention network (GAT) to predict lncRNA-miRNA interactions in animals. First, we construct a meta-path similarity matrix based on known lncRNA-miRNA interaction information. Then, we use GAT to aggregate the constructed meta-path similarity matrix and the computed Gaussian kernel similarity matrix to update the feature matrix with neighbourhood information. Finally, a scoring module is used for prediction. By comparing with three state-of-the-art algorithms, MPGK-LMI achieves the best results in terms of performance, with AUC value of 0.9077, AUPR of 0.9327, ACC of 0.9080, F1-score of 0.9143 and precision of 0.8739. These results validate the effectiveness and reliability of MPGK-LMI. Additionally, we conduct detailed case studies to demonstrate the effectiveness and feasibility of our approach in practical applications. Through these empirical results, we gain deeper insights into the functional roles and mechanisms of lncRNA-miRNA interactions, providing significant breakthroughs and advancements in this field of research. In summary, our method not only outperforms others in terms of performance but also establishes its practicality and reliability in biological research through real-case analysis, offering strong support and guidance for future studies and applications.

Extensive research has recognized the significant roles of non-coding RNAs (ncRNAs) in various cellular pathophysiological processes and their association with diverse diseases, including atrial septal defect (ASD), one of the most prevalent congenital heart diseases. This systematic review aims to explore the intricate involvement and significance of ncRNAs in the pathogenesis and progression of ASD.

Four databases (PubMed, Embase, Scopus, and the Web of Science) were searched systematically up to June 19, 2023, with no year restriction. The risk of bias assessment was evaluated using the Newcastle-Ottawa scale.

The present systematic review included thirteen studies with a collective study population of 874 individuals diagnosed with ASD, 21 parents of ASD patients, and 22 pregnant women carrying ASD fetuses. Our analysis revealed evidence linking five long ncRNAs (STX18-AS1, HOTAIR, AA709223, BX478947, and Moshe) and several microRNAs (hsa-miR-19a, hsa-miR-19b, hsa-miR-375, hsa-miR-29c, miR-29, miR-143/145, miR-17-92, miR-106b-25, and miR-503/424, miR-9, miR-30a, miR-196a2, miR-139-5p, hsa-let-7a, hsa-let-7b, and hsa-miR-486) to ASD progression, corresponding to previous studies.

NcRNAs play a crucial role in unraveling the underlying mechanisms of ASD, contributing to both biomarker discovery and therapeutic advancements. This systematic review sheds light on the mechanisms of action of key ncRNAs involved in ASD progression, providing valuable insights for future research in this field.

Cancer stem cells (CSCs) are one of the cell types that account for cancer heterogeneity. The cancer cells arrest in G0 and generate non-CSC progeny through self-renewal and pluripotency, resulting in tumor recurrence, metastasis, and resistance to chemotherapy. They can stimulate tumor relapse and re-grow a metastatic tumor. So, CSCs is a promising target for eradicating tumors, and developing an anti-CSCs therapy has been considered. In recent years competing endogenous RNA (ceRNA) has emerged as a significant class of post-transcriptional regulators that affect gene expression via competition for microRNA (miRNA) binding. Furthermore, aberrant ceRNA expression is associated with tumor progression. Recent findings show that ceRNA network can cause tumor progression through the effect on CSCs. To overcome therapeutic resistance due to CSCs, we need to improve our current understanding of the mechanisms by which ceRNAs are implicated in CSC-related relapse. Thus, this review was designed to discuss the role of ceRNAs in CSCs' function. Targeting ceRNAs may open the path for new cancer therapeutic targets and can be used in clinical research.

The PI3K/AKT/GSK-3β signaling pathway plays a pivotal role in numerous physiological and pathological processes, including cell proliferation, apoptosis, differentiation, and metabolic regulation. Aberrant activation of the PI3K/AKT pathway is intricately linked to development of tumor. GSK-3β, belonging to the serine/threonine protein kinase family, is crucial in the pathogenesis of liver cancer. As a key rate-limiting enzyme in the glucose metabolism pathway, GSK-3β significantly impacts the growth, proliferation, metastasis, and apoptosis of liver cancer cells. It is also implicated in chemotherapy resistance. Elevated expression of GSK-3β diminishes the sensitivity of liver cancer cells to chemotherapeutic agents, thereby playing a substantial role in the development of drug resistance. Consequently, targeting of GSK-3β, particularly within the PI3K/AKT signaling pathway, is regarded as a promising therapeutic strategy for liver cancer. The precise identification and subsequent modulation of this pathway represent a substantial potential for innovative clinical interventions in the management of liver cancer.

This is a mini-review capturing the views and opinions of selected participants at the 2021 IEEE BIBM 3rd Annual LncRNA Workshop, held in Dubai, UAE. The views and opinions are expressed on five broad themes related to problems in lncRNA, namely, challenges in the computational analysis of lncRNAs, lncRNAs and cancer, lncRNAs in sports, lncRNAs and COVID-19, and lncRNAs in human brain activity.

Osteoclasts, which are responsible for bone resorption, are specialized multinucleated cells generated from monocyte/macrophage progenitor cells or hematopoietic stem cells (HSCs). Physiological bone remodeling can become pathological, such as osteoporosis, when osteoclastogenesis is out of balance. Thousands of long noncoding RNAs (lncRNAs) influence important molecular and biological processes. Recent research has revealed gene expression regulation function that numerous lncRNAs regulate nuclear domain organization, genome stability. Furthermore, the research of lncRNAs has substantial clinical implications for the treatment of existing and new diseases.

In this review, we gather the most recent research on lncRNAs and their potential for basic research and clinical applications in osteoclast and osteoporosis. We also discuss the findings here in order to fully understand the role of lncRNAs in osteoclast differentiation and osteoporosis, as well as to provide a solid basis for future research exploring associated mechanisms and treatments.

LncRNA has been considered as an important role in the regulation of osteoclast differentiation and osteoporosis. It is exciting to investigate pathophysiological processes in osteoporosis and the therapeutic potential of lncRNAs. We hope that this review will offer promising prospects for the development of precision and individualized approaches to treatment.

Aberrant long noncoding RNA (lncRNA) expression is linked to varied pathological processes and malignant tumors, and lncRNA can serve as potential disease biomarkers. Herein, we demonstrate the autonomous enzymatic synthesis of functional nucleic acids for sensitive measurement of lncRNA in human lung tissues on the basis of multiple primer generation-mediated rolling circle amplification (mPG-RCA). This assay involves two padlock probes that act as both a detection probe for recognizing target lncRNA and a domain for producing complementary DNAzyme. Two padlock probes can hybridize with target lncRNA at different sites, followed by ligation to form a circular template with the aid of RNA ligase. The circular template can initiate mPG-RCA to generate abundant Mg2+-dependent DNAzymes that can specifically cleave signal probes to induce the recovery of Cy3 fluorescence. The inherent characteristics of ligase-based ligation reaction and DNAzymes endow this assay with excellent specificity, and the introduction of multiple padlock probes endows this assay with high sensitivity. This strategy can rapidly and sensitively measure lncRNA with a wide linear range of 1 fM - 1 nM and a detection limit of 678 aM within 1.5 h, and it shows distinct advantages of simplicity and immobilization-free without the need of precise temperature control and tedious procedures of nanomaterial preparation. Moreover, it enables accurate measurement of lncRNA level in normal cells and malignant tumor cells as well as differentiation of lncRNA expressions in tissues of non-small cell lung cancer (NSCLC) patients and normal individuals, with promising applications in biomedical studies and disease diagnosis.

Cancer chimeric, or fusion, transcripts are thought to most frequently appear due to chromosomal aberrations that combine moieties of unrelated normal genes. When being expressed, this results in chimeric RNAs having upstream and downstream parts relatively to the breakpoint position for the 5'- and 3'-fusion components, respectively. As many other types of cancer mutations, fusion genes can be of either driver or passenger type. The driver fusions may have pivotal roles in malignisation by regulating survival, growth, and proliferation of tumor cells, whereas the passenger fusions most likely have no specific function in cancer. The majority of research on fusion gene formation events is concentrated on identifying fusion proteins through chimeric transcripts. However, contemporary studies evidence that fusion events involving non-coding RNA (ncRNA) genes may also have strong oncogenic potential. In this review we highlight most frequent classes of ncRNAs fusions and summarize current understanding of their functional roles. In many cases, cancer ncRNA fusion can result in altered concentration of the non-coding RNA itself, or it can promote protein expression from the protein-coding fusion moiety. Differential splicing, in turn, can enrich the repertoire of cancer chimeric transcripts, e.g. as observed for the fusions of circular RNAs and long non-coding RNAs. These and other ncRNA fusions are being increasingly recognized as cancer biomarkers and even potential therapeutic targets. Finally, we discuss the use of ncRNA fusion genes in the context of cancer detection and therapy.

In the cell nucleus, genomic DNA is surrounded by nonmembranous nuclear bodies. This might result from specific regions of the genome being transcribed into long noncoding RNAs (lncRNAs), which tend to remain at the sites of their own transcription. The lncRNAs seed the nuclear bodies by recruiting and concentrating proteins and RNAs, which undergo liquid-liquid-phase separation, and form molecular condensates, the so-called nuclear bodies. These nuclear bodies may provide appropriate environments for gene activation or repression. Notably, lncRNAs also contribute to three-dimensional genome structure by mediating long-range chromatin interactions. In this review, we discuss the mechanisms by which lncRNAs regulate gene expression through shaping chromatin and nuclear architectures. We also explore lncRNAs' potential as a therapeutic target for cancer, because lncRNAs are often expressed in a disease-specific manner.

Polycystic ovary syndrome (PCOS) is the most common condition affecting women of reproductive age globally. PCOS continues to be the largest contributing factor to female infertility despite significant progress in our knowledge of the molecular underpinnings and treatment of the condition. The fact that PCOS is a very diverse condition makes it one of the key reasons why we haven't been able to overcome it. Non-coding RNAs (ncRNAs) are implicated in the development of PCOS, according to growing evidence. However, it is unclear how the complex regulatory relationships between the many ncRNA types contribute to the growth of this malignancy. Competing endogenous RNA (ceRNA), a recently identified mechanism in the RNA world, suggests regulatory interactions between various RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). Recent studies on PCOS have shown that dysregulation of multiple ceRNA networks (ceRNETs) between these ncRNAs plays crucial roles in developing the defining characteristics of PCOS development. And it is believed that such a finding may open a new door for a deeper comprehension of PCOS's unexplored facets. In addition, it may be able to provide fresh biomarkers and effective therapy targets for PCOS. This review will go over the body of information that exists about the primary roles of ceRNETs before highlighting the developing involvement of several newly found ceRNETs in a number of PCOS characteristics.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

Highly polar and charged molecules, such as oligonucleotides, face significant barriers in crossing the cell membrane to access the cytoplasm. To address this problem, we developed a light-triggered twistable tetraphenylethene (TPE) derivative, TPE-C-N, to facilitate the intracellular delivery of charged molecules through an endocytosis-independent pathway. The central double bond of TPE in TPE-C-N is planar in the ground state but becomes twisted in the excited state. Under light irradiation, this planar-to-twisted structural change induces continuous cell membrane disturbances. Such disturbance does not lead to permanent damage to the cell membrane. TPE-C-N significantly enhanced the intracellular delivery of negatively charged molecules under light irradiation when endocytosis was inhibited through low-temperature treatment, confirming the endocytosis-independent nature of this delivery method. We have successfully demonstrated that the TPE-C-N-mediated light-controllable method can efficiently promote the intracellular delivery of charged molecules, such as peptides and oligonucleotides, with molecular weights ranging from 1000 to 5000 Da.

Long non-coding RNAs (lncRNAs) outnumber protein-coding transcripts, but their functions remain largely unknown. In this Review, we discuss the emerging roles of lncRNAs in the control of gene transcription. Some of the best characterized lncRNAs have essential transcription cis-regulatory functions that cannot be easily accomplished by DNA-interacting transcription factors, such as XIST, which controls X-chromosome inactivation, or imprinted lncRNAs that direct allele-specific repression. A growing number of lncRNA transcription units, including CHASERR, PVT1 and HASTER (also known as HNF1A-AS1) act as transcription-stabilizing elements that fine-tune the activity of dosage-sensitive genes that encode transcription factors. Genetic experiments have shown that defects in such transcription stabilizers often cause severe phenotypes. Other lncRNAs, such as lincRNA-p21 (also known as Trp53cor1) and Maenli (Gm29348) contribute to local activation of gene transcription, whereas distinct lncRNAs influence gene transcription in trans. We discuss findings of lncRNAs that elicit a function through either activation of their transcription, transcript elongation and processing or the lncRNA molecule itself. We also discuss emerging evidence of lncRNA involvement in human diseases, and their potential as therapeutic targets.

RNA targeting, specifically with small molecules, is a relatively new and rapidly emerging avenue with the promise to expand the target space in the drug discovery field. From being "disregarded" as an "undruggable" messenger molecule to FDA approval of an RNA-targeting small-molecule drug Risdiplam, a radical change in perspective toward RNA has been observed in the past decade. RNAs serve important regulatory functions beyond canonical protein synthesis, and their dysregulation has been reported in many diseases. A deeper understanding of RNA biology reveals that RNA molecules can adopt a variety of structures, carrying defined binding pockets that can accommodate small-molecule drugs. Due to its functional diversity and structural complexity, RNA can be perceived as a prospective target for therapeutic intervention. This perspective highlights the proof of concept of RNA-small-molecule interactions, exemplified by targeting of various transcripts with functional modulators. The advent of RNA-oriented knowledge would help expedite drug discovery.

Long noncoding RNAs (lncRNAs) are major components of cellular transcripts that are emerging as important players in various biological pathways. Due to their specific expression and functional diversity in a variety of cancers, lncRNAs have promising applications in cancer diagnosis, prognosis, and therapy. Studies have shown that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) with high specificity and accuracy has the potential to become biomarkers in cancers. LncRNA DGCR5 can be noninvasively extracted from body fluids, tissues, and cells, and can be used as independent or auxiliary biomarkers to improve the accuracy of diagnosis or prognosis. Now, the underlying mechanisms of lncRNAs such as DGCR5 were explored as therapeutic targets, which have been investigated in clinical trials of several cancers. The DGCR5 lacks an appropriate animal model, which is necessary to gain greater knowledge of their functions. While some studies on the uses of DGCR5 have been carried out, the small sample size makes them unreliable. In this review, we presented a compilation of recent publications addressing the potential of lncRNA DGCR5 that could be considered as biomarkers or therapeutic targets, with the hopes of providing promised implications for future cancer therapy.

Wilms' tumor (WT) is a rare kidney cancer that primarily affects children. Exosomes are extracellular vesicles that cargo nucleic acids, proteins,etc. for cellular communication. Long non-coding RNAs (lncRNAs) have utility as biomarkers for cancer diagnosis, prognosis, and disease monitoring. We hypothesize that expression of lncRNA, metastasis-associated lung adenocarcinoma transcript-1(MALAT1), is dysregulated and possibly trafficked within exosomes to influence the tissue microenvironment for metastasis and recurrence of WT.

We investigated the expression of MALAT1 in thirty WT samples by qPCR. Exosomes were isolated using a precipitated and affinity-binding-based kit, and characterized using TEM, NTA, and DLS.

Mean number of exosomes was 9.01×108/mL in primary culture, 1.64×108/mL in urine, and 4.65×108/plasma:400µl. Average yield of total RNA was 1.28µg (primary-culture supernatant:1ml), 1.47µg (Urine:1ml), 1.65µg (Plasma:400 µL). We quantified MALAT1 in exosomes derived from these sources in patients of WT. Expression of MALAT1 was significantly downregulated (p=0.008) in WT samples.

This is the first study that demonstrated the presence of lncRNA MALAT1 in various invasive and non-invasive samples of patients with WT(primary tissue culture, urine, and plasma samples).

Hepatocellular carcinoma (HCC) is a prevalent liver malignancy with complex etiology and generally poor prognosis. Recently, long non-coding RNAs (lncRNAs), non-protein-coding RNA molecules exceeding 200 nucleotides, have emerged as pivotal players in HCC, influencing its initiation, progression, invasion, and metastasis. These lncRNAs modulate gene expression at epigenetic, transcriptional, and post-transcriptional levels, actively participating in the pathological and physiological processes of HCC. Understanding the intricate relationship between lncRNAs and HCC is important for improving prognosis and reducing mortality. This review summarizes advancements in elucidating the role of lncRNAs in HCC pathogenesis.

Long non-coding RNAs (lncRNAs) have begun to receive overdue attention for their regulatory roles in gene expression and other cellular processes. Although most lncRNAs are lowly expressed and tissue-specific, notable exceptions include MALAT1 and its genomic neighbor NEAT1, two highly and ubiquitously expressed oncogenes with roles in transcriptional regulation and RNA splicing. Previous studies have suggested that NEAT1 is found only in mammals, while MALAT1 is present in all gnathostomes (jawed vertebrates) except birds. Here we show that these assertions are incomplete, likely due to the challenges associated with properly identifying these two lncRNAs. Using phylogenetic analysis and structure-aware annotation of publicly available genomic and RNA-seq coverage data, we show that NEAT1 is a common feature of tetrapod genomes except birds and squamates. Conversely, we identify MALAT1 in representative species of all major gnathostome clades, including birds. Our in-depth examination of MALAT1, NEAT1, and their genomic context in a wide range of vertebrate species allows us to reconstruct the series of events that led to the formation of the locus containing these genes in taxa from cartilaginous fish to mammals. This evolutionary history includes the independent loss of NEAT1 in birds and squamates, since NEAT1 is found in the closest living relatives of both clades (crocodilians and tuataras, respectively). These data clarify the origins and relationships of MALAT1 and NEAT1 and highlight an opportunity to study the change and continuity in lncRNA structure and function over deep evolutionary time.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that deals with dopaminergic deficiency in Substantia nigra pars compact (SNpc) region of the brain. Dopaminergic deficiency manifests into motor dysfunction. Alpha-synuclein protein aggregation is the source for inception of the pathology. Motor symptoms include rigidity, akinesia, tremor and gait dysfunction. Pre-motor symptoms are also seen in early stage of the disease; however, they are not distinguishable. Lack of early diagnosis in PD pathology poses a major challenge for development of disease modifying therapeutics. Substantial neuronal loss has already been occurred before the clinical manifestations appear and hence, it becomes impossible to halt the disease progression. Current diagnostics are majorly based on the clinical symptoms and thus fail to detect early progression of the disease. Thus, there is need for early diagnosis of PD, for detection of the disease at its inception. This will facilitate the effective use of therapies that halt the progression and will make remission possible. Many novel biomarkers are being developed that include blood-based biomarker, CSF biomarker. Other than that, there are non-invasive techniques that can detect biomarkers. We aim to discuss potential role of these new age biomarkers and their association with PD pathogenesis in this review.

Long non-coding RNAs (lncRNAs) are significant contributors in maintaining genomic integrity through epigenetic regulation. LncRNAs can interact with chromatin-modifying complexes in both cis and trans pathways, drawing them to specific genomic loci and influencing gene expression via DNA methylation, histone modifications, and chromatin remodeling. They can also operate as building blocks to assemble different chromatin-modifying components, facilitating their interactions and gene regulatory functions. Deregulation of these molecules has been associated with various human diseases, including cancer, cardiovascular disease, and neurological disorders. Thus, lncRNAs are implicated as potential diagnostic indicators and therapeutic targets. This review discusses the current understanding of how lncRNAs mediate epigenetic control, genomic integrity, and their putative functions in disease pathogenesis.

Prostate cancer (PC) is a leading cause of cancer-related death in males worldwide. Neuroendocrine differentiation (NED) is a feature of PC that often goes undetected and is associated with poor patient outcomes. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs/miRs), and messenger RNAs (mRNAs) play important roles in the development and progression of PC.

In this study, we used transcriptome sequencing and bioinformatics analysis to identify key regulators of NED in PC. Specifically, we examined the expression of PC-related lncRNAs, miRNAs, and mRNAs in PC cells and correlated these findings with NED phenotypes.

Our data revealed that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and zinc finger protein 91 (ZFP91) were upregulated in PC, while miR-216a-5p was down-regulated. Ectopic expression of MALAT1 induced NED and promoted malignant phenotypes of PC cells. Furthermore, we found that MALAT1 competitively bound to miR-216a-5p, upregulated ZFP91, and promoted the degradation of forkhead box A1 (FOXA1), a key gene involved in NED of PC.

Taken together, these results suggest that MALAT1 plays an oncogenic role in NED and metastasis of PC via the miR-216a-5p/ZFP91/FOXA1 pathway. Our study highlights the potential of targeting this pathway as a novel therapeutic strategy for PC.

The process of alternative splicing (AS) is widely deregulated in a variety of cancers. Splicing is dependent upon splicing factors. Recently, several long noncoding RNAs (lncRNAs) have been shown to regulate AS by directly/indirectly interacting with splicing factors. This review focuses on the regulation of AS by lncRNAs through their interaction with splicing factors. AS mis-regulation caused by either mutation in splicing factors or deregulated expression of splicing factors and lncRNAs has been shown to be involved in cancer development and progression, making aberrant splicing, splicing factors and lncRNA suitable targets for cancer therapy. This review also addresses some of the current approaches used to target AS, splicing factors and lncRNAs. Finally, we discuss research challenges, some of the unanswered questions in the field and provide recommendations to advance understanding of the nexus of lncRNAs, AS and splicing factors in cancer.

For several decades, most lung cancer investigations have focused on the search for mutations in candidate genes; however, in the last decade, due to the fact that most of the human genome is occupied by sequences that do not code for proteins, much attention has been paid to non-coding RNAs (ncRNAs) that perform regulatory functions. In this review, we principally focused on recent studies of the function, regulatory mechanisms, and therapeutic potential of ncRNAs including microRNA (miRNA), long ncRNA (lncRNA), and circular RNA (circRNA) in different types of lung cancer.

Melanoma is a rare but highly lethal type of skin cancer whose incidence is increasing globally. Melanoma is characterized by high resistance to therapy and relapse. Despite significant advances in the treatment of metastatic melanoma, many patients experience progression due to resistance mechanisms. Epigenetic changes, including alterations in chromatin remodeling, DNA methylation, histone modifications, and non-coding RNA rearrangements, contribute to neoplastic transformation, metastasis, and drug resistance in melanoma. This review summarizes current research on epigenetic mechanisms in melanoma and their therapeutic potential. Specifically, we discuss the role of histone acetylation and methylation in gene expression regulation and melanoma pathobiology, as well as the promising results of HDAC inhibitors and DNMT inhibitors in clinical trials. We also examine the dysregulation of non-coding RNA, particularly miRNAs, and their potential as targets for melanoma therapy. Finally, we highlight the challenges of epigenetic therapies, such as the complexity of epigenetic mechanisms combined with immunotherapies and the need for combination therapies to overcome drug resistance. In conclusion, epigenetic changes may be reversible, and the use of combination therapy between traditional therapies and epigenetically targeted drugs could be a viable solution to reverse the increasing number of patients who develop treatment resistance or even prevent it. While several clinical trials are underway, the complexity of these mechanisms presents a significant challenge to the development of effective therapies. Further research is needed to fully understand the role of epigenetic mechanisms in melanoma and to develop more effective and targeted therapies.

Long noncoding RNAs (lncRNAs) are key regulators in numerous pathological and physiological processes, and their aberrant expression is implicated in many diseases. Herein, we develop a programmable feedback network with continuously activatable molecular beacon (MB) fluorescence for one-step quantification of mammalian-metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) in clinical breast tissues. We introduce a functional MB with three domains, including a substrate for lncRNA MALAT1 recognition, a template for strand displacement amplification (SDA), and a reporter for signal output with FAM fluorescence being quenched by BHQ1. When MALAT1 is present, it recognizes and unfolds the MB, leading to the recovery of FAM fluorescence. Once the MB is opened, multiple rounds of SDA reaction are automatically initiated by recruiting primer, KF DNA polymerase, and Nt.BbvCI nicking enzyme, inducing the opening of more MBs and the dissociation of more FAM/BHQ1 pairs. Consequently, a feedback network is constructed through multicycle cascade SDA, achieving the exponential accumulation of fluorescence signals for accurate quantification of MALAT1. In this assay, only two oligonucleotides (i.e., MB and primer) are involved for the establishment of a feedback amplification network, greatly simplifying the design of the reaction system. Moreover, this assay requires only one step to realize the isothermal exponential amplification for real-time monitoring of MALAT1 with attomolar sensitivity. This assay displays single-base mismatch selectivity with high anti-interference capability, and it can further quantify endogenous MALAT1 at the single-cell level and differentiate MALAT1 expression between breast cancer patient tissues and healthy person tissues.

Long noncoding RNAs (lncRNAs) play crucial roles in regulating various hallmarks in cancers. Triple-negative (Estrogen receptor, ER; Human epidermal growth factor receptor 2, HER2; Progesterone receptor, PR) breast cancer (TNBC) is the most aggressive form of breast cancers with a poor prognosis and no available molecular targeted therapy.

We reviewed the current literature on the roles of lncRNAs in the pathogenesis, therapy resistance, and prognosis of patients with TBNC.

LncRNAs are associated with TNBC pathogenesis, therapy resistance, and prognosis. For example, lncRNAs such as small nucleolar RNA host gene 12 (SNHG12), highly upregulated in liver cancer (HULC) HOX transcript antisense intergenic RNA (HOTAIR), lincRNA-regulator of reprogramming (LincRNA-ROR), etc., are aberrantly expressed in TNBC and are involved in the pathogenesis of the disease. LncRNAs act as a decoy, scaffold, or sponge to regulate the expression of genes, miRNAs, and transcription factors associated with pathogenesis and progression of TNBC. Moreover, lncRNAs such as ferritin heavy chain 1 pseudogene 3 (FTH1P3), BMP/OP-responsive gene (BORG) contributes to the therapy resistance property of TNBC through activating ABCB1 (ATP-binding cassette subfamily B member 1) drug efflux pumps by increasing DNA repair capacity or by inducing signaling pathway involved in therapeutic resistance.

In this review, we outline the functions of various lncRNAs along with their molecular mechanisms involved in the pathogenesis, therapeutic resistance of TBNC. Also, the prognostic implications of lncRNAs in patients with TNBC is illustrated. Moreover, potential strategies targeting lncRNAs against highly aggressive TNBC is discussed in this review.

Breast cancer (BC) is a major public health concern, and identifying new biomarkers and therapeutic targets is critical to improving patient outcomes. MALAT1, a long noncoding RNA, has emerged as a promising candidate due to its overexpression in BC and the associated poor prognosis. Understanding the role of MALAT1 in BC progression is paramount for the development of effective therapeutic strategies.

This review delves into the structure and function of MALAT1, and examines its expression pattern in breast cancer (BC) and its association with different BC subtypes. This review focuses on the interactions between MALAT1 and microRNAs (miRNAs) and the various signaling pathways involved in BC. Furthermore, this study investigates the influence of MALAT1 on the BC tumor microenvironment and the possible influence of MALAT1 on immune checkpoint regulation. This study also sheds light the role of MALAT1 in breast cancer resistance.

MALAT1 has been shown to play a key role in the progression of BC, highlighting its importance as a potential therapeutic target. Further studies are needed to elucidate the underlying molecular mechanisms by which MALAT1 contributes to the development of BC. In combination with standard therapy, there is a need to evaluates the potential of treatments targeting MALAT1, which may lead to improved treatment outcomes. Moreover, study of MALAT1 as a diagnostic and prognostic marker promises improved BC management. Continued efforts to decipher the functional role of MALAT1 and explore its clinical utility are critical to advancing the BC research field.

In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies focus on single genes that are usually repressed. Due to the genomic binding properties of both macromolecules, we wondered whether there are binding sites shared by PRC2 and MALAT1. Using public genome-binding datasets for PRC2 and MALAT1 derived from independent ChIP- and CHART-seq experiments performed with the breast cancer cell line MCF7, we searched for regions containing PRC2 and MALAT1 overlapping peaks. Peak calls for each molecule were performed using MACS2 and then overlapping peaks were identified by bedtools intersect. Using this approach, we identified 1293 genomic sites where PRC2 and MALAT1 concur. Interestingly, 54.75% of those sites are within gene promoter regions (<3000 bases from the TSS). These analyses were also linked with the transcription profiles of MCF7 cells, obtained from public RNA-seq data. Hence, it is suggested that MALAT1 and PRC2 can concomitantly bind to promoters of actively-transcribed genes in MCF7 cells. Gene ontology analyses revealed an enrichment of genes related to categories including cancer malignancy and epigenetic regulation. Thus, by re-visiting occupancy and transcriptomic data, we identified a key gene subset controlled by the collaboration of MALAT1 and PRC2.

The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation is the main event in the development and progression of human cancer, including melanoma and recent studies have shown that MALAT1 has a significant impact on the regulation of gene and protein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK and ERK in melanoma is largely unknown. We demonstrate the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma. Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin. Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced tumor growth in an NRAS-mutant melanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects. Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated.