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Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is aggressive and lethal. Although there is an urgent need for effective therapeutics in treating pancreatic cancer, none of the targeted therapies tested in clinical trials to date significantly improve its outcome. PORCN inhibitors show efficacy in pre-clinical models of Wnt-addicted cancers including RNF43-mutant pancreatic cancers and have advanced to clinical trials. In this study, we aimed to develop drug combination strategies to further enhance the therapeutic efficacy of the PORCN inhibitor ETC-159. To identify additional druggable vulnerabilities in Wnt-driven pancreatic cancers, we performed an in vivo CRISPR loss-of-function screen. CTNNB1, KRAS, and MYC were re-identified as key oncogenic drivers. Notably, glucose metabolism pathway genes were important in vivo but less so in vitro. Knockout of multiple genes regulating PI3K/mTOR signaling impacted the growth of Wnt-driven pancreatic cancer cells in vivo. Importantly, multiple PI3K/mTOR pathway inhibitors in combination with ETC-159 synergistically suppressed the growth of multiple Wnt-addicted cancer cell lines in soft agar. Furthermore, the combination of the PORCN inhibitor ETC-159 and the pan-PI3K inhibitor GDC-0941 potently suppressed the in vivo growth of RNF43-mutant pancreatic cancer xenografts. This was largely due to enhanced suppressive effects on both cell proliferation and glucose metabolism. These findings demonstrate that dual PORCN and PI3K/mTOR inhibition is a potential strategy for treating Wnt-driven pancreatic cancers.

Wnt signaling maintains diverse adult stem cell compartments and is implicated in chemotherapy resistance in cancer. PORCN inhibitors that block Wnt secretion have proven effective in Wnt-addicted preclinical cancer models and are in clinical trials. In a survey for potential combination therapies, we found that Wnt inhibition synergizes with the PARP inhibitor olaparib in Wnt-addicted cancers. Mechanistically, we find that multiple genes in the homologous recombination and Fanconi anemia repair pathways, including BRCA1, FANCD2, and RAD51 are dependent on Wnt/β-catenin signaling in Wnt-high cancers, and treatment with a PORCN inhibitor creates a BRCA-like state. This coherent regulation of DNA repair genes occurs via a Wnt/β-catenin/MYBL2 axis. Importantly, this pathway also functions in intestinal crypts, where high expression of BRCA and Fanconi anemia genes is seen in intestinal stem cells, with further upregulation in Wnt high APCmin mutant polyps. Our findings suggest a general paradigm that Wnt/β-catenin signaling enhances DNA repair in stem cells and cancers to maintain genomic integrity. Conversely, interventions that block Wnt signaling may sensitize cancers to radiation and other DNA damaging agents.

[Image: see text] SMYD3 is a histone methyltransferase that regulates gene transcription, and its overexpression is associated with multiple human cancers. A novel class of tetrahydroacridine compounds which inhibit SMYD3 through a covalent mechanism of action is identified. Optimization of these irreversible inhibitors resulted in the discovery of 4-chloroquinolines, a new class of covalent warheads. Tool compound 29 exhibits high potency by inhibiting SMYD3′s enzymatic activity and showing antiproliferative activity against HepG2 in 3D cell culture. Our findings suggest that covalent inhibition of SMYD3 may have an impact on SMYD3 biology by affecting expression levels, and this warrants further exploration.

Long non-coding RNAs and microRNAs control gene expression to determine central nervous system development and function. Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule that plays an important role in neurite outgrowth during neuronal development and its precise expression is crucial for correct brain development. The data described here is related to the research article titled “A long non-coding RNA, BC048612 and a microRNA, miR-203 coordinate the gene expression of Neuronal growth regulator 1 (NEGR1) adhesion protein” [1]. This data article contains detailed bioinformatics analysis of genetic signatures at the Negr1 gene locus retrieved from the UCSC genome browser. This approach could be adopted to identify putative regulatory non-coding RNAs in other tissues and diseases. Keywords: Bioinformatics, Long non-coding RNA, MicroRNA, Negr1, Regulation

The regulatory roles for non-coding RNAs, the long non-coding RNAs and microRNAs, are emerging as crucial determinants of central nervous system development and function. Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule that has been shown to play an important role in neurite outgrowth during neuronal development. Precise expression of the Negr1 gene is crucial for proper brain development and is dysregulated during brain injury. Hence, we attempted to elucidate the non-coding RNAs that control Negr1 gene expression. A long non-coding RNA, BC048612, transcribed from the bidirectional GC-rich Negr1 gene promoter was found to influence Negr1 mRNA expression. In vitro knockdown of the long non-coding RNA resulted in significant down-regulation of Negr1 mRNA expression, NEGR1 protein levels and neurite length whereas over-expression enhanced Negr1 mRNA expression, NEGR1 protein levels and increased neurite length. Meanwhile, another non-coding RNA, microRNA-203, was found to target the 3' untranslated region of the Negr1 mRNA. Inhibition of microRNA-203 led to increased expression of Negr1 mRNA, elevated NEGR1 protein levels and increased neurite length. Conversely, microRNA-203 over-expression decreased the level of Negr1 mRNA, NEGR1 protein and neurite length. Neither microRNA-203 nor the long non-coding RNA, BC048612 could influence each other's expression. Hence, the long non-coding RNA, BC048612, and microRNA-203 were determined to be positive and negative regulators of Negr1 gene expression respectively. These processes have a direct effect on NEGR1 protein levels and neurite length, thus highlighting the importance of the regulatory non-coding RNAs in modulating Negr1 gene expression for precise neuronal development.

Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure–activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.

Aim The potential diagnostic utility of circulating microRNAs in heart failure (HF) or in distinguishing HF with reduced vs. preserved left ventricular ejection fraction (HFREF and HFPEF, respectively) is unclear. We sought to identify microRNAs suitable for diagnosis of HF and for distinguishing both HFREF and HFPEF from non-HF controls and HFREF from HFPEF. Methods and results MicroRNA profiling performed on whole blood and corresponding plasma samples of 28 controls, 39 HFREF and 19 HFPEF identified 344 microRNAs to be dysregulated among the three groups. Further analysis using an independent cohort of 30 controls, 30 HFREF and 30 HFPEF, presented 12 microRNAs with diagnostic potential for one or both HF phenotypes. Of these, miR-1233, -183-3p, -190a, -193b-3p, -193b-5p, -211-5p, -494, and -671-5p distinguished HF from controls. Altered levels of miR-125a-5p, -183-3p, -193b-3p, -211-5p, -494, -638, and -671-5p were found in HFREF while levels of miR-1233, -183-3p, -190a, -193b-3p, -193b-5p, and -545-5p distinguished HFPEF from controls. Four microRNAs (miR-125a-5p, -190a, -550a-5p, and -638) distinguished HFREF from HFPEF. Selective microRNA panels showed stronger discriminative power than N-terminal pro-brain natriuretic peptide (NT-proBNP). In addition, individual or multiple microRNAs used in combination with NT-proBNP increased NT-proBNP's discriminative performance, achieving perfect intergroup distinction. Pathway analysis revealed that the altered microRNAs expression was associated with several mechanisms of potential significance in HF. Conclusions We report specific microRNAs as potential biomarkers in distinguishing HF from non-HF controls and in differentiating between HFREF and HFPEF.

MicroRNAs have been identified as key regulators of gene expression and thus their potential in disease diagnostics, prognosis and therapy is being actively pursued. Deregulation of microRNAs in cerebral pathogenesis has been reported to a limited extent in both animal models and human. Due to the complexity of the pathology, identifying stroke specific microRNAs has been a challenge. This study shows that microRNA profiles reflect not only the temporal progression of stroke but also the specific etiologies. A panel of 32 microRNAs, which could differentiate stroke etiologies during acute phase was identified and verified using a customized TaqMan Low Density Array (TLDA). Furthermore we also found 5 microRNAs, miR-125b-2*, -27a*, -422a, -488 and -627 to be consistently altered in acute stroke irrespective of age or severity or confounding metabolic complications. Differential expression of these 5 microRNAs was also observed in rat stroke models. Hence, their specificity to the stroke pathology emphasizes the possibility of developing these microRNAs into accurate and useful tools for diagnosis of stroke.

Coordinated interplay of dysregulated microRNAs in isolated metabolic disorder is implicated in the pathogenesis of metabolic syndrome.The objective of the study was to characterize microRNA expression in the blood and exosomes of individuals with metabolic syndrome and compare them with those manifesting one of the metabolic vascular risk factors (type 2 diabetes, hypercholesterolemia, or hypertension). RESEARCH DESIGN/SETTING/PARTICIPANTS: A total of 265 participants were recruited in a health screening and characterized into distinct groups as follows: 1) healthy controls (n = 46); 2) metabolic syndrome (n = 50); 3) type 2 diabetes (n = 50); 4) hypercholesterolemia (n = 89); and 5) hypertension (n = 30). Total RNA was subjected to microRNA profiling, and a panel of significantly dysregulated microRNAs was validated using quantitative PCR.Analysis of profiling data characterized unique pools of miRNAs that could categorize the different risk factors of metabolic syndrome.We have identified miR-197, miR-23a, and miR-509-5p as potential contributors of dyslipidemia in metabolic syndrome (correlation with body mass index; P = 0.029, 0.021, and 0.042, respectively) and miR-130a and miR-195 as contributors of hypertension (correlation with blood pressure; P = 0.019 and 0.045, respectively). A plausible association of miR-27a and miR-320a with metabolic syndrome and type 2 diabetes patients has also been found because these miRNAs remained dysregulated in both cases (correlation with fasting glucose; P = 0.010 and 0.016, respectively).Significant dysregulation of seven candidate microRNAs has been found to be associated with risks involved in the manifestation of metabolic syndrome.

Aquaporins facilitate efficient diffusion of water across cellular membranes, and water homeostasis is critically important in conditions such as cerebral edema. Changes in aquaporin 1 and 4 expression in the brain are associated with cerebral edema, and the lack of water channel modulators is often highlighted. Here we present evidence of an endogenous modulator of aquaporin 1 and 4. We identify miR-320a as a potential modulator of aquaporin 1 and 4 and explore the possibility of using miR-320a to alter the expression of aquaporin 1 and 4 in normal and ischemic conditions. We show that precursor miR-320a can function as an inhibitor, whereas anti-miR-320a can act as an activator of aquaporin 1 and 4 expressions. We have also shown that anti-miR-320a could bring about a reduction of infarct volume in cerebral ischemia with a concomitant increase in aquaporins 1 and 4 mRNA and protein expression.

Aberrations in WNT signaling, a pathway regulated by a family of secreted glycoproteins known as WNTs, is implicated as a cause for cancer. Post-translational modification of WNTs by porcupine is critical for their activity and eventual activation of the WNT pathway. ETC-159 is an orally available, potent porcupine inhibitor. Addition of ETC-159 suppresses cancer proliferation in several cell lines by blocking the secretion and activity of all WNTs. Nevertheless, tumor growth is driven by complex molecular interactions that dysregulate several pathways at any one time. Thus, early drug discovery studies have increasingly evolved to target multiple molecules or pathways. As therapeutic approaches using combinations of drugs directed at multiple targets can improve treatment response, in this study we explored the possibility of identifying compounds that are synergistic with ETC-159. Unlike conventional two-dimensional combination drug screening, we used the three-dimensional soft agar colony formation assays for the study. Dose-response curves were first independently established to obtain the EC50 ranges for each drug, before proceeding to combination treatments. Using the Chou-Talalay Drug Combination Software, CompuSyn, we identified several inhibitors, which target the PI3K pathway, to act synergistically with ETC-159 in pancreatic cell lines HPAF-II, ASPC-1 and CFPAC-I. Similar treatments in nonpancreatic cell lines indicated that the observed synergism was not cell-line specific, hence highlighting the applicability of such combination treatments for different cancers. Citation Format: Sugunavathi Sepramaniam, Xin Hui Chew, Kao Chin Ngeow, May Ann Lee. ETC159, a porcupine inhibitor, exhibits synergism with PI3K inhibitors in 3-dimensional cell culture [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2939.

Pathogenesis of cerebral ischemia has so far been described in the context of proteins and the pathways that they regulate. The discovery of biomarkers has also been focussed mainly on proteins and to some extent on the mRNAs that encode them. The knowledge on the role of microRNAs in understanding the pathogenesis of cerebral ischemia is still at its infancy. In this study, using rat models subjected to middle cerebral artery occlusion, we have profiled the microRNAs at different reperfusion times (0 to 48 h) to understand the progression of cerebral ischemia. We have also attempted to correlate the expression of microRNAs to treatment with an NMDA antagonist (MK801) and to protein expression with the hope of demonstrating the potential use of microRNAs as early biomarkers of stroke.

Programmed cell death (PCD), is a highly regulated and sophisticated cellular mechanism that commits cell to isolated death fate. PCD has been implicated in the pathogenesis of numerous neurodegenerative disorders. Countless molecular events underlie this phenomenon, with each playing a crucial role in death commitment. A precedent event, apoptotic volume decrease (AVD), is ubiquitously observed in various forms of PCD induced by different cellular insults. Under physiological conditions, cells when subjected to osmotic fluctuations will undergo regulatory volume increase/decrease (RVI/RVD) to achieve homeostatic balance with neurons in the brain being additionally protected by the blood-brain-barrier. However, during AVD following apoptotic trigger, cell undergoes anistonic shrinkage that involves the loss of water and ions, particularly monovalent ions e.g. K(+), Na(+) and Cl(-). It is worthwhile to concentrate on the molecular implications underlying the loss of these cellular components which posed to be significant and crucial in the successful propagation of the apoptotic signals. Microarray and real-time PCR analyses demonstrated several ion and water channel genes are regulated upon the onset of lactacystin (a proteosomal inhibitor)-mediated apoptosis. A time course study revealed that gene expressions of water and ion channels are being modulated just prior to apoptosis, some of which are aquaporin 4 and 9, potassium channels and chloride channels. In this review, we shall looked into the molecular protein machineries involved in the execution of AVD in the central nervous system (CNS), and focus on the significance of movements of each cellular component in affecting PCD commitment, thus provide some pharmacological advantages in the global apoptotic cell death.

Background Dengue is the most common arboviral illness worldwide. While most infected patients recover, a proportion of them develop severe complications or fatality. Nevertheless, the pathophysiological mechanisms which distinguish the disease severity and associated complications are not clearly understood. We studied blood profiles of dengue patients in order to identify microRNAs that could play a role in these pathophysiological mechanisms. Methods Blood samples from 26 dengue-infected patients were collected within 0–14 days of infection. Together with samples obtained from six healthy individuals, microRNA profiles were generated to identify significantly altered microRNAs upon dengue infection. Profiles of patients with influenza were also used to determine the disease specificity of these altered microRNAs. Their discriminative power to distinguish dengue from influenza was then tested statistically. Results Several significantly altered microRNAs were identified in patients with dengue. Twelve microRNAs were specifically altered upon acute dengue whereas 14 microRNAs exhibited similar expression between dengue and influenza. Seventeen microRNAs which could potentially distinguish dengue-related complications were also identified. Expression of miR-24-1-5p, miR-512-5p and miR-4640-3p distinguished mild dengue from those exhibiting liver complications whereas miR-383 was significantly upregulated in mild dengue compared to those diagnosed as severe dengue with fluid accumulation. Conclusions We identified two panels of microRNAs – one specific for dengue and the other common to dengue and influenza. We also report on the differentially expressed microRNAs in patients with mild versus severe dengue, which could be the basis for the complications seen in them.

In obese individuals, a high efflux of glycerol from accumulated fat in adipose tissue into the liver is known to be associated with the development of type 2 diabetes. Aquaporin 9 (AQP9) is an aquaglyceroporin which serves as the primary route of hepatic glycerol uptake for gluconeogenesis. Hence, development of AQP9 blockers/regulators may be of potential benefit in controlling hyperglycaemia especially in obese and diabetic individuals. HTS13286 was recently identified as a specific AQP9 inhibitor, even so its limited solubility renders the molecule unsuitable for in vivo application. microRNAs are naturally occurring gene regulators that are often associated with various diseases. The feasibility in selective modulation of microRNAs has introduced a new paradigm for therapeutic applications. In this study, we explore the possibility of using microRNAs to regulate AQP9 expression and eventually glycerolbased gluconeogenesis. In silico prediction of microRNAs targeting the 3’ untranslated region of AQP9 was conducted using miRWalk database. Among the list of potential microRNAs, miR-22 and miR-23a were shortlisted for their high expression in liver and further confirmed to interact with AQP9 via luciferase assay. Over-expression of miR-22 or miR- 23a was able to reduce AQP9 expression (mRNA and protein) and ultimately inhibit glycerol-based gluconeogenesis in HepG2 cells. Livers of diabetic rats were also observed to exhibit an inverse correlation between miR-22, miR-23a and AQP9 expression. As negative modulators of AQP9 expression, miR-22 and miR-23a suggest a potential role in regulating glycerol entry into hepatocytes which could be beneficial in managing glycerol-dependent hyperglycaemic conditions.

Neuronal development is a pro-survival process that involves neurite growth, synaptogenesis, synaptic and neuronal pruning. During development, these processes can be controlled by temporal gene expression that is orchestrated by both long non-coding RNAs and microRNAs. To examine the interplay between these different components of the transcriptome during neuronal differentiation, we carried out mRNA, long non-coding RNA and microRNA expression profiling on maturing primary neurons. Subsequent gene ontology analysis revealed regulation of axonogenesis and dendritogenesis processes by these differentially expressed mRNAs and non-coding RNAs. Temporally regulated mRNAs and their associated long non-coding RNAs were significantly over-represented in proliferation and differentiation associated signalling, cell adhesion and neurotrophin signalling pathways. Verification of expression of the Axin2, Prkcb, Cntn1, Ncam1, Negr1, Nrxn1 and Sh2b3 mRNAs and their respective long non-coding RNAs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile to the maturation process, thus suggesting their role(s) in maintaining neuronal structure and function. Furthermore, we propose that expression of the cell adhesion molecules, Ncam1 and Negr1 might be tightly regulated by both long non-coding RNAs and microRNAs.

The 3' UTR of insulin has been identified as a critical region that confers mRNA stability, which is crucial for promoting transcription in response to glucose challenge. miRNAs are endogenously encoded non-coding RNAs that function as regulators of gene expression. This regulatory function is generally mediated by complementary binding to the 3'UTR of its mRNA targets that affects subsequent translational process. Genes involved in the regulation of glucose homeostasis, particularly in insulin production, have been found as targets of several miRNAs. Yet, no direct miRNA-based regulators of insulin biosynthesis have been identified. In this study, identification of possible miRNA-based regulators of insulin production is explored. Members of a miRNA family, miR-25 and miR-92a, are found as direct modulators of insulin expression. Overexpression of miR-25 or miR-92a reduced insulin expression while inhibition of miR-25 and miR-92a expression using corresponding antagomiRs promoted insulin expression and ultimately enhanced glucose-induced insulin secretion. Furthermore, suppression of insulin secretion by pre miR-9 could be attenuated by treatment with anti-miR-25 or miR-92a. Interestingly, we found the binding site of miR-25 and miR-92a to overlap with that of PTBP1, an important RNA binding molecule that stabilizes insulin mRNA for translation. Despite the increase in PTBP1 protein in the pancreas of diabetic rats, we observed insulin expression to be reduced alongside upregulation of miR-25 and miR-92a, suggesting an intricate regulation of insulin (bio)synthesis at its mRNA level.

Over the past decade, scientific discoveries have highlighted new roles for a unique class of non-coding RNAs. Transcribed from the genome, these non-coding RNAs have been implicated in determining the biological complexity seen in mammals by acting as transcriptional and translational regulators. Non-coding RNAs, which can be sub-classified into long non-coding RNAs, microRNAs, PIWI-interacting RNAs and several others, are widely expressed in the nervous system with roles in neurogenesis, development and maintenance of the neuronal phenotype. Perturbations of these non-coding transcripts have been observed in ischemic preconditioning as well as ischemic brain injury with characterization of the mechanisms by which they confer toxicity. Their dysregulation may also confer pathogenic conditions in neurovascular diseases. A better understanding of their expression patterns and functions has uncovered the potential use of these riboregulators as neuroprotectants to antagonize the detrimental molecular events taking place upon ischemic-reperfusion injury. In this review, we discuss the various roles of non-coding RNAs in brain development and their mechanisms of gene regulation in relation to ischemic brain injury. We will also address the future directions and open questions for identifying promising non-coding RNAs that could eventually serve as potential neuroprotectants against ischemic brain injury.

Aquaporins (AQPs) are transmembrane water channels ubiquitously expressed in mammalian tissues. They play prominent roles in maintaining cellular fluid balance. Although expression of AQP1, -3, -4, -5, -8, -9, and -11 has been reported in the central nervous system, it is AQP4 that is predominately expressed. Its importance in fluid regulation in cerebral edema conditions has been highlighted in several studies, and we have also shown that translational regulation of AQP4 by miR-320a could prove to be useful in infarct volume reduction in middle cerebral artery occluded rat brain. There is evidence for the existence of two AQP4 transcripts (M1 and M23) in the brain arising from two alternative promoters. Because the AQP4 M1 isoform exhibits greater water permeability, in this study, we explored the possibility of microRNA-based transcriptional regulation of the AQP4 M1 promoter. Using RegRNA software, we identified 34 microRNAs predicted to target the AQP4 M1 promoter region. MicroRNA profiling, quantitative stem-loop PCR, and luciferase reporter assays revealed that miR-130a, -152, -668, -939, and -1280, which were highly expressed in astrocytes, could regulate the promoter activity. Of these, miR-130a was identified as a strong transcriptional repressor of the AQP4 M1 isoform. In vivo studies revealed that LNA(TM) anti-miR-130a could up-regulate the AQP4 M1 transcript and its protein to bring about a reduction in cerebral infarct and promote recovery.

MicroRNAs (miRNAs) are endogenous short (20–22 nucleotides) non-coding RNA molecules that mediate gene expression. This is an important regulatory mechanism to modulate fundamental cellular processes such as differentiation, proliferation, death, metabolism, and pathophysiology of many diseases. The miRNA expression profile of the kidney differs greatly from that of other organs, as well as between the different regions in the kidney. In kidneys, miRNAs are indispensable for development and homeostasis. In this review, we explore the involvement of miRNAs in the regulation of blood pressure, hormone, water, and ion balance pertaining to kidney homeostasis. We also highlight their importance in renal pathophysiology, such as in polycystic disease, diabetic nephropathy, nephrogenic diabetes insipidus, hypertension, renal cancer, and kidney fibrosis (epithelial–mesenchymal transition). In addition, we highlight the need for further investigations on miRNA-based studies in the development of diagnostic, prognostic, and therapeutic tools for renal diseases.

Background The methods currently available for diagnosis and prognosis of cerebral ischaemia still require further improvements. Micro-RNAs (small non-coding RNAs) have been recently reported as useful biomarkers in diseases such as cancer and diabetes. We therefore carried out microRNA (miRNA) profiling from peripheral blood to detect and identify characteristic patterns in ischaemic stroke. Methods/Principal Findings The ischaemic stroke patients aged between 18–49 years, characterized based on World Health Organization clinical criteria were further classified according to TOAST classification, a) Large-vessel atherosclerosis [n = 8] b) Small-vessel disease [n = 3] c) Cardioembolism [n = 5] d) Undetermined cause [n = 3]. The patients' functional status at the time of blood sampling (at the outpatient clinics) was evaluated with the modified Rankin Scale (mRS). Blood samples from normal (n = 5) individuals were used as controls. Total RNA extracted from whole blood was subjected to miroRNA profiling and real-time PCR analysis. miRNAs that are implicated in the endothelial/vascular function, erythropoiesis, angiogenesis and neural function showed differential expression profile as compared to the normal control. Interestingly, miRNAs that are involved in hypoxic conditions have also been found in our miRNA profiles. Conclusion We demonstrate that the peripheral blood miRNAs and their profiles can be developed as biomarkers in diagnosis and prognosis of cerebral ischaemic stroke. The dysregulated miRNAs have been detectable even after several months from the onset of stroke in what is usually regarded as neurologically stable patients.

Aquaporins (AQPs) are a family of small hydrophobic, integral membrane proteins that are expressed in all living organisms and play critical roles in controlling the water flow into and out of cells. So far, 13 different AQPs have been identified in mammals (AQP 0-12). AQPs have recently been implicated in various diseases such as cancer, cataract, brain oedema, gallstone disease and nephrogenic diabetes insipidus, as well as in the development of obesity and polycystic kidney disease. Interfering with the expression of AQPs will undoubtedly have therapeutic applications. Hence, in this review, the authors look at each AQP and its association with various pathological conditions in humans and demonstrate that they form potential targets for the treatment of such diseases.