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Background: Ribosome biogenesis protein BRX1 homolog (BRIX1) is critically required for the synthesis of the 60S ribosome subunit. However, the role and mechanism of BRIX1 in colorectal cancer (CRC) remain unclear. Methods: Kyoto Encyclopedia of Gene and Genome pathway and Gene Ontology analyses were used for bioinformatics analysis. The rRNA levels were detected in CRC tissues and cells. Nascent RNA synthesis was detected via cellular immunofluorescence. The correlation was analyzed between patient Positron Emission Tomography‐Computed Tomography (PET–CT) values and their BRIX1 expression. The extracellular acidification rate (ECAR) and oxygen consumption rate were determined via live metabolic analyses. Polysome fractions were collected for BRIX1 mRNA used in translation. The orthotopic model and Cell Counting Kit‐8 (CCK8) assay were used to assess BRIX1 function in CRC. Results: BRIX1 is a core protein involved in ribosome‐related pathway changes in CRC. Gene Ontology analysis showed that BRIX1 was primarily enriched in ribosome assembly and ribosome biogenesis pathways. In fresh CRC tissue, rRNA levels (5S, 5.8S, 18S and 28S) were higher in the BRIX1 high‐expression group than in the BRIX1 low‐expression group. Similarly, BRIX1 knockdown significantly decreased rRNA levels for 5S, 5.8S, 18S and 28S in CRC cells, whereas overexpression of BRIX1 significantly increased these levels. In addition, BRIX1 knockdown inhibited nascent RNA synthesis in CRC cells. In clinical data analysis, BRIX1 expression was related to the glucose uptake in PET–CT. BRIX1 knockdown significantly decreased the ECAR value, glucose uptake and lactic acid production in CRC cells, whereas BRIX1 overexpression significantly increased these. Furthermore, BRIX1 knockdown significantly decreased the protein expression of GLUT1, whereas BRIX1 overexpression significantly increased this; however, expression of BRIX1 mRNA was unaffected in either case. Blocking glycolysis by si‐GLUT1 or galactose reversed BRIX1 promotion of glycolysis and cell proliferation in CRC cells. [ABSTRACT FROM AUTHOR]

The ultralow concentration of nucleic acids in complex biological samples requires fluorescence probes with high specificity and sensitivity. Herein, a new kind of spherical nucleic acids (SNAs) is developed by using fluorescent π‐conjugated polymers (FCPs) as a light‐harvesting antenna to enhance the signal transduction of nucleic acid detection. Specifically, amphiphilic DNA‐grafted FCPs are synthesized and self‐assemble into FCP‐SNA structures. Tuning the hydrophobicity of the graft copolymer can adjust the size and light‐harvesting capability of the FCP‐SNAs. We observe that more efficient signal amplification occurs in larger FCP‐SNAs, as more chromophores are involved, and the energy transfer can go beyond the Förster radius. Accordingly, the optimized FCP‐SNA shows an antenna effect of up to 37‐fold signal amplification and the limit of detection down to 1.7 pM in microRNA detection. Consequently, the FCP‐SNA is applied to amplified in situ nucleic acid detecting and imaging at the single‐cell level. [ABSTRACT FROM AUTHOR]

Mitochondrial Pyruvate Carrier 1 (MPC1), one of the rate-limiting proteins involved in glycolysis metabolism, has been demonstrated as a tumor inhibitor in several cancers. This study was conducted with the aim of exploring the role and underlying mechanisms of MPC2 in colorectal cancer (CRC). Here, we found that MPC2 expression was decreased in CRC samples. According to the analysis on our TMA data, lower expression of MPC2 is correlated with a higher incidence of distant metastasis and lymph node invasion, bigger tumor size, low survival rate of patients, and advanced T stages. Functionally, in vivo/vitro experiments showed that MPC2 knockdown induced CRC cell proliferation and growth, while MPC2 overexpression inhibited the proliferation and growth of CRC. Further study demonstrated that MPC2 knockdown resulted in aerobic glycolysis in CRC cells. Similarly, MPC2 overexpression in CRC cells also caused inhibited aerobic glycolysis. Further study found that MPC2 knockdown in CRC cell lines activated the mTOR signaling pathway, and the addition of rapamycin reversed the promoting effect of MPC2 knockdown on CRC proliferation and glycolysis. Likewise, the addition of MHY1485 also reversed the MPC2 overexpression's role in hindering aerobic glycolysis in CRC cells. Collectively, our study established that low expression of MPC2 led to CRC growth as well as aerobic glycolysis through the regulation of the mTOR pathway in CRC cells, indicating a potential biomarker and therapy target for CRC. [ABSTRACT FROM AUTHOR]