Jessica Matts, Ph.D.’s Post

interesting paper - the link between metabolism and cGAS-mediated immunity!

Collab🚨: CRI's McBrayer Lab contributed to a discovery published in Science Magazine from the Manguso Lab & Bardeesy Lab at Mass General Hospital Cancer Center that defines a new #cancer-causing mechanism associated with IDH1 mutations (the most commonly mutated metabolic gene across cancers). From Sam McBrayer, Ph.D.: "They found that IDH1 mutations repress expression and sensing of transposable viral elements in the genome that can trigger innate immune signaling in brain and liver cancers. "Drugs that inhibit IDH1 mutant enzymes can reverse this process, leading to anti-tumor immune responses. These findings provide new insights into how IDH1 mutations, as well as drugs that target these mutations, regulate cancer growth." Read it here: https://lnkd.in/gheTrga8 #relentlessdiscovery #CancerResearch

𝘚𝘤𝘪𝘦𝘯𝘵𝘪𝘴𝘵𝘴 𝘧𝘰𝘶𝘯𝘥 𝘵𝘩𝘢𝘵 𝘴𝘪𝘭𝘦𝘯𝘤𝘪𝘯𝘨 𝘰𝘧 𝘢 𝘬𝘦𝘺 𝘨𝘦𝘯𝘦 𝘥𝘳𝘪𝘷𝘦𝘴 𝘱𝘢𝘯𝘤𝘳𝘦𝘢𝘵𝘪𝘤 𝘤𝘢𝘯𝘤𝘦𝘳 𝘢𝘨𝘨𝘳𝘦𝘴𝘴𝘪𝘷𝘦𝘯𝘦𝘴𝘴 🧬 Pancreatic cancer is an aggressive cancer that is often difficult to detect and treat. Researchers have been working to understand the genetic factors that contribute to the development and progression of this disease. A recent study has shed light on the role of a key gene, HNF4A, in driving pancreatic cancer aggressiveness. The development and progression of cancer is caused by mutations of genetic components. Mutations that turn on or turn off (silence) key genes, such as KRAS, CDKN2A, TP53, and SMAD4, are related to pancreatic cancer. However, the specific genetic cause is unknown, as every patient has unique differences in their tumors. A mutation that causes cancer in one patient may not cause cancer in another. Genes can be silenced through a range of different mechanisms. One process is called DNA methylation, which adds a methyl group to a specific DNA molecule. This essentially tells your body to ignore this gene, preventing its expression. This can be beneficial for a cancer as genes that suppress tumor development can be ignored. UK and US researchers collaborated to analyze methylation in pancreatic cancer tissues and cell lines. They identified that a gene named HNF4A is hypermethylated in cancer but not in a healthy pancreas. The true function of HNF4A in pancreatic cancer is unclear, but research suggests it acts as a tumor suppressor. Loss of a gene that aims to suppress the development of tumors allows tumors free reign to grow uncontrollably. Researchers also found that this gene was silenced in the earliest stages of cancer. This discovery opens a door for early treatment that may save lives, as early intervention targeting the HNF4A gene may restore its function and stop the progression of cancer. Interestingly, another paper found that a high-fat high-sugar diet suppresses HNF4A in mice and drives liver disease and diabetes. Combined, these papers highlight the importance of prioritizing a healthy, balanced diet. Pancreatic cancer HNF4A: https://lnkd.in/eck8CKE7 High-fat high-sugar HNF4A: https://lnkd.in/enstRrxV #pancreaticcancer #diet #genetics #science #methylation #cancer #research

Like pieces in a puzzle, more evidence is accumulating for the "moonlighting" of oncoproteins such as Myc. As we map these proteins to more and more oncopathways, their diverse roles reveal that tumor heterogeneity reflects oncoprotein "moonlighting" and therefore, the diverse interaction networks that drive cancer development and growth. The transcription factor MYC plays a significant role in cancer progression by driving various hallmarks of cancer development. While MYC is known to promote oncogenic transcription by binding to active promoters, it has also been observed to invade distal enhancers, albeit with previously assumed low gene-regulatory potential. However, new findings suggest that MYC directly regulates enhancer activity to promote cancer type-specific gene programs that are predictive of poor patient prognosis. This regulation involves MYC inducing transcription of enhancer RNA through the recruitment of RNA polymerase II (RNAPII), rather than regulating RNAPII pause-release, which is typical at promoters. This induction process is facilitated by MYC-induced H3K9 demethylation and acetylation by GCN5, leading to enhancer-specific BRD4 recruitment through its bromodomains, ultimately facilitating RNAPII recruitment. The study proposes that MYC drives prognostic cancer type-specific gene programs through the induction of an enhancer-specific epigenetic switch, which could be targeted therapeutically by BET and GCN5 inhibitors. These findings shed light on the complex regulatory mechanisms involving MYC in cancer progression and suggest potential therapeutic targets for intervention.

Cervical cancer (CC), caused by human papillomavirus (HPV), is a leading cause of female malignancies worldwide. Therefore, understanding the underlying mechanisms of CC development and identifying novel therapeutic targets are significantly important. Cisplatin resistance is a significant challenge in the management of CC. Recent studies highlighted the critical role of long non-coding RNAs (lncRNAs) in modulation of cisplatin resistance. This comprehensive review aims to collect the current understanding roles of lncRNAs and their involvement in cisplatin resistance in CC by highlighting key processes of cancer progression, including apoptosis, proliferation, angiogenesis and epithelial-to-mesenchymal transition (EMT). We discussed the role of lncRNA in CC resistance to cisplatin through molecular pathways and examined gene expression changes. We also discussed treatment strategies and factors that reduce CC resistance to cisplatin by targeting them. https://lnkd.in/gfseS625

Our research provides crucial insights into pancreatic ductal adenocarcinoma (PDAC). Hypoxia, a defining characteristic of PDAC, correlates with disease severity, influencing treatment response, invasiveness, and immunosuppression. Utilizing the Buffa gene signature, we pinpointed LGALS3 as a pivotal gene linked to high hypoxia levels. Elevated hypoxia is associated with reduced levels of T cells, NK cells, and dendritic cells, along with increased immunosuppressive molecules. These findings propose innovative strategies for advancing PDAC immunotherapy by targeting both hypoxia and specific immune elements. Kudos to the team's exceptional work, particularly acknowledging Hassan Sadozai's contributions. https://lnkd.in/es9rQuXv #pancreaticcancer #immunology #immunotherapy #teamcollaboration #teameffort #cancertreatment #cancerresearch #medicaladvancements #transcriptomics #collaborations #interdisciplinary #leadership #leadershipdevelopment #machinelearning

I am elated to share a publication from my Ph.D. work at Prof. Arun Kumar's lab in the Indian Institute of Science (IISc). We have accomplished a serendipitous feat in discovering a non-canonical functional role of a small non-coding RNA, miR-617, in regulating DDX27 and exploring its therapeutic potential in oral cancer treatment. Counterintuitively, miR-617 positively regulates its gene target DDX27 by interacting with its promoter instead of the 3’UTR of DDX27 mRNA. This observation is even more intriguing because miR-617 has putative binding sites in both 3’UTR and promoter of DDX27. Furthermore, this study provides valuable insight into the complex molecular mechanism of oral cancer pathogenesis. This is one of the 15 miRNAs to date that interacts with the promoter DNA of gene target to cause transcriptional gene activation. I request you all to give it a read and share your valuable thoughts on it. The link to the study is as follows: https://lnkd.in/g3NEm4aU.

A microRNA down regulates a gene, that's the norm we have always lived with, right?? Well, there're few of them activating genes as well!! Didn't know about it?? Read more below: Another piece of extraordinary research from our lab solely done by Dr. Neelanjana Sarkar.. Congratulations on the publication!!

Identifying the mechanisms underlying cancer resistance to therapy is crucial for advancing treatment strategies. Pathogenic mutations in homologous recombination repair (HRR) genes are established biomarkers for the effectiveness of platinum (Pt)-based chemotherapy and poly ADP ribose polymerase inhibitors (PARPi). However, the dynamics of HRR reversion mutations, which may indicate therapy resistance, remain not fully understood. Addressing this gap, a Geneseeq-collaborated study analyzed secondary HRR gene mutations in a comprehensive pan-cancer dataset of approximately 13,000 patients who underwent targeted next-generation sequencing by GeneseeqPrime™. This investigation enhances our understanding of cancer's adaptive mechanisms in response to therapy, advocating a crucial shift towards more personalized and dynamic treatment strategies. It emphasizes the necessity of adapting to cancer's genetic evolution to stay ahead in the ongoing fight against the disease. #cancerresearch #cancergenomics #homologousrecombinationrepair #cancertreatment Read more about this study: https://lnkd.in/gMEZFU5y Learn more about GeneseeqPrime™: https://lnkd.in/gwA8QkUW

📃Scientific paper: MBTPS2 acts as a regulator of lipogenesis and cholesterol synthesis through SREBP signalling in prostate cancer Abstract: Background Prostate cancer is the most common cancer in men in the developed world, with most deaths caused by advanced and metastatic disease which has no curative options. Here, we identified Mbtps2 alteration to be associated with metastatic disease in an unbiased in vivo screen and demonstrated its regulation of fatty acid and cholesterol metabolism. Methods The Sleeping Beauty transposon system was used to randomly alter gene expression in the Pten ^ Null murine prostate. MBTPS2 was knocked down by siRNA in LNCaP, DU145 and PC3 cell lines, which were then phenotypically investigated. RNA-Seq was performed on LNCaP cells lacking MBTPS2 , and pathways validated by qPCR. Cholesterol metabolism was investigated by Filipin III staining. Results Mbtps2 was identified in our transposon-mediated in vivo screen to be associated with metastatic prostate cancer. Silencing of MBTPS2 expression in LNCaP, DU145 and PC3 human prostate cancer cells reduced proliferation and colony forming growth in vitro. Knockdown of MBTPS2 expression in LNCaP cells impaired cholesterol synthesis and uptake along with reduced expression of key regulators of fatty acid synthesis, namely FASN and ACACA . Conclusion MBTPS2 is implicated in progressive prostate cancer and may mechanistically involve its effects on fatty acid and cholesterol metabolism. Continued on ES/IODE ➡️ https://etcse.fr/OMyIB ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.