As one of the primary members of SWI/SNF chromatin remodeling complexes, ARID1A contains frequent loss-of-function mutations in many types of cancers. However, the molecular mechanisms underlying ARID1A deficiency in cancer biology remain to be investigated. Using breast cancer as a model, we report that silencing ARID1A significantly increased cellular proliferation and migration. Mechanistically, primarily functioning as a transcriptional repressor, loss of ARID1A profoundly alters histone modifications and the transcriptome. Notably, ARID1A inhibited the expression of a long non-coding RNA, UCA1, by regulating chromatin access of the transcription factor CEBPα. Restoration experiments showed that UCA1 mediates the functions of ARID1A that induces loss of cellular proliferation and migration. Together, our findings characterize ARID1A as a key tumor-suppressor gene in breast cancer through cooperation with CEBPα, and loss-of-function mutations of ARID1A activates UCA1.

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Phytobioactive compounds are plant secondary metabolites and bioactive compounds abundantly present in medicinal plants and have remarkable therapeutic potential. Oxidative stress and antibiotic resistance are major causes of present‐day ailments such as diabetes, atherosclerosis, cardiovascular disorders, cancer, and inflammation. The data for this review were collected from Google Scholar, PubMed, Directory of Open Access Journals (DOAJ), and Science Direct by using keywords: “Medicinal plants, Phytobioactive compounds, Polyphenols, Alkaloids, Carotenoids etc.” Several studies have reported the pharmacological and therapeutic potential of the phytobioactives. Polyphenols, alkaloids, terpenes, and polysaccharides isolated from medicinal plants showed remarkable antioxidant, anticancer, cytotoxic, anti‐inflammatory, cardioprotective, hepatoprotective, immunomodulatory, neuroprotective, and antidiabetic activities. This literature review was planned to provide comprehensive insight into the biopharmacological and therapeutic potential of phytobioactive compounds. The techniques used for the extraction and isolation of phytobioactive compounds, and bioassays required for their biological activities such as antioxidant, antimicrobial, anti‐inflammatory, and cytotoxic activities, have been discussed. Characterization techniques for the structural elucidation of phytobioactive compounds such as HPLC, TLC, FTIR, GC–MS/MS, and NMR have also been discussed. This review concludes that phytobioactive compounds may be used as potential alternative to synthetic compounds as therapeutic agents for the treatment of various diseases.

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The epithelial cell adhesion molecule (EpCAM) is considered an essential proliferation signature in cancer. In the current research study, qPCR induced expression of EpCAM was noted in acute lymphoblastic leukemia (ALL) cases. Costunolide, a sesquiterpene lactone found in crepe ginger and lettuce, is a medicinal herb with anticancer properties. Expression of EpCAM and its downstream target genes (Myc and TERT) wasdownregulated upon treatment with costunolide in Jurkat cells. A significant change in the telomere length of Jurkat cells was not noted at 72 h of costunolide treatment. An in silico study revealed hydrophobic interactions between EpCAM extracellular domain and Myc bHLH with costunolide. Reduced expression of NFκB, a transcription factor of EpCAM, Myc, and TERT in costunolide-treated Jurkat cells, suggested that costunolide inhibits gene expression by targeting NFκB and its downstream targets. Overall, the study proposes that costunolide could be a promising therapeutic biomolecule for leukemia.

Telomere length (TEL) regulation is important for genome stability and is governed by the coordinated role of shelterin proteins, telomerase (TERT), and CST (CTC1/OBFC1/TEN1) complex. Previous studies have shown the association of telomerase expression with the risk of acute lymphoblastic leukemia (ALL). However, no data are available for CST association with the ALL. The current pilot study was designed to evaluate the CST expression levels in ALL. In total, 350 subjects were recruited, including 250 ALL cases and 100 controls. The subjects were stratified by age and categorized into pediatrics (1–18 years) and adults (19–54 years). TEL and expression patterns of CTC1, OBFC1, and TERT genes were determined by qPCR. The univariable logistic regression analysis was performed to determine the association of gene expression with ALL, and the results were adjusted for age and sex in multivariable analyses. Pediatric and adult cases did not reflect any change in telomere lengths relative to controls. However, expression of CTC1, OBFC1, and TERT genes were induced among ALL cases. Multivariable logistic regression analyses showed association of CTC1 with ALL in pediatric [β estimate (standard error (SE)= −0.013 (0.007), p = 0.049, and adults [0.053 (0.023), p = 0.025]. The association of CTC1 remained significant when taken together with OBFC1 and TERT in a multivariable model. Furthermore, CTC1 showed significant association with B-cell ALL [−0.057(0.017), p = 0.002) and T-cell ALL [−0.050 (0.018), p = 0.008] in pediatric group while no such association was noted in adults. Together, our findings demonstrated that telomere modulating genes, particularly CTC1, are strongly associated with ALL. Therefore, CTC1 can potentially be used as a risk biomarker for the identification of ALL in both pediatrics and adults.

S87 delay, intellectual disability, microcephaly, delayed brain myelination, and recurrent seizures, ultimately resulting in the death of most patients before the age of twenty. However, the function of UBA5 in the nervous system and how mutation of UBA5 results in disease was not known. To investigate the pathophysiology associated with UBA5 mutation and to identify pathways that could reduce disease progression we are using the zebrafish. We show that uba5 loss of function in zebrafish leads to significant decrease in locomotor activity, recapitulating the motor dysfunction observed in UBA5 patients. Notably, the motor impairment is not preceded by damage to the overall neuronal network and muscle morphology. However, electron microscopy reveals signs of degradation and aggregates in the nerves innervating the skeletal muscle of uba5 mutants. This finding suggests that there may be an early sub-clinical phenotype in the peripheral nervous system that could contribute to the pathology observed in UBA5 patients. We also identify a dramatic reduction in growth. We describe the identification of the pathways disrupted by the loss of Uba5 , explaining the epileptic symptoms, growth defects, and neurodegeneration observed in patients.

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