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Sequencing data of a novel piperine derivative HJ-4 against colorectal cancer

ABSTRACT: In order to explore the mechanism of HJ-4, we used RNA-seq technology to extract and analyze the total RNA of cells treated with DMSO and HJ-4, and analyzed the RNA data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282967 | GEO | 2024/11/28

REPOSITORIES: GEO

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Sequencing data of a novel piperine derivative HJ-23 against colorectal cancer

Project description:In order to explore the mechanism of HJ-23, we used RNA-seq technology to extract and analyze the total RNA of cells treated with DMSO and HJ-23, and analyzed the RNA data.

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Sequencing data of a novel piperine derivative HJ-23 against colorectal cancer

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Sequencing data of a novel piperine derivative HJ-4 against colorectal cancer

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A Novel Piperine Derivative Inhibits Colorectal Cancer Progression by Modulating EMT Signaling Pathways: An Integrated Transcriptomic and Machine Learning Analysis

Project description:Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies worldwide. The epithelial-mesenchymal transition (EMT) plays a critical role in tumor invasion and metastasis. Piperine, a natural alkaloid, has demonstrated antitumor activity; however, its low bioavailability limits clinical application. HJJ_3_5, a novel piperine derivative synthesized and validated by our research group, exhibits potent antitumor effects against colorectal cancer cells. In addition to its strong cytotoxicity, HJJ_3_5 disrupts key metastatic processes, including DNA replication, cell migration, invasion, and adhesion, showcasing its multifaceted mechanism of action. In vivo, HJJ_3_5 shows significant efficacy in the CAM model, effectively inhibiting tumor growth and angiogenesis, underscoring its potential as a powerful anti-cancer agent. At the molecular level, comprehensive transcriptomic analysis reveals that HJJ_3_5 significantly downregulates the EMT pathway. Notably, machine learning algorithms identify six core EMT-related genes (COL12A1, PJA2, VCAN, MEF2C, DPYD, and DDR2) as pivotal drivers of cancer progression, with their expression strongly associated with poor clinical outcomes. Single-cell RNA sequencing further reveals that these genes are predominantly expressed in fibroblasts and myofibroblasts, key players in the EMT process and metastasis. These findings position HJJ_3_5 as a promising therapeutic candidate, offering a targeted and potent approach to halting the relentless progression of colorectal cancer.

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The archaeal ATPase PINA interacts with the helicase Hjm via its carboxyl terminal KH domain remodeling and processing replication fork and Holliday junction

Project description:PINA is a novel ATPase and DNA helicase highly conserved in archaea, the third domain of life. The PINA from Sulfolobus islandicus (SisPINA) forms a hexameric ring, promotes Holliday junction (HJ) migration, and physically and functionally interacts with Hjc, the HJ specific endonuclease. Here, we show that SisPINA has strong physical interaction with Hjm (Hel308a), a helicase presumably targeting replication forks. In vitro biochemical analysis revealed that Hjm, Hjc, and SisPINA are able to coordinate HJ migration and cleavage in a concerted way. Deletion of the carboxyl 13 amino acid residues abolishes the interaction between SisPINA and Hjm. Crystal structure analysis showed that the carboxyl 70 amino acid residues fold into a type II KH domain which, in other proteins, functions in binding RNA and ssDNA. The KH domain not only mediates the interactions of PINA with Hjm and Hjc but also regulates the hexameric assembly of PINA. Our results collectively suggest possible mechanisms for SisPINA, Hjm, and Hjc to work together in replication fork regression, HJ formation, and HJ cleavage.

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