From metabolism to malignancy: the multifaceted role of PGC1α in cancer.

PGC1α, a central player in mitochondrial biology, holds a complex role in the metabolic shifts seen in cancer cells. While its dysregulation is common across major cancers, its impact varies. In some cases, downregulation promotes aerobic glycolysis and progression, whereas in others, overexpression escalates respiration and aggression. PGC1α's interactions with distinct signaling pathways and transcription factors further diversify its roles, often in a tissue-specific manner. Understanding these multifaceted functions could unlock innovative therapeutic strategies. However, challenges exist in managing the metabolic adaptability of cancer cells and refining PGC1α-targeted approaches. This review aims to collate and present the current knowledge on the expression patterns, regulators, binding partners, and roles of PGC1α in diverse cancers. We examined PGC1α's tissue-specific functions and elucidated its dual nature as both a potential tumor suppressor and an oncogenic collaborator. In cancers where PGC1α is tumor-suppressive, reinstating its levels could halt cell proliferation and invasion, and make the cells more receptive to chemotherapy. In cancers where the opposite is true, halting PGC1α's upregulation can be beneficial as it promotes oxidative phosphorylation, allows cancer cells to adapt to stress, and promotes a more aggressive cancer phenotype. Thus, to target PGC1α effectively, understanding its nuanced role in each cancer subtype is indispensable. This can pave the way for significant strides in the field of oncology.

Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression.

The mitogen activated protein kinase (MAPK) pathway has been reported to be involved in many cancer developments. Normally, MAPK activity is self-limited between rapid phosphorylation and dephosphorylation. In abnormal conditions, however, this dynamic equilibrium is broken, trigging tumor-suppressing or -promoting roles. While dual-specificity MAPK phosphatases (MKP/DUSPs) are important for cascade control in MAPK pathway, their role in colorectal cancer (CRC) remains largely unknown. Here, we investigated lnc-FAM84B-4 and DUSP1 to systematically elucidate their underlying roles in MAPK singling pathway and functions in CRC. Upregulated lnc-FAM84B-4 was identified by re-mining CRC microarray. Functional assays were performed in vitro and in vivo. RNA-Seq, RNA pull-down, and RIP assays were used to investigate the mechanisms of Lnc-FAM84B-4 in regulating expression of DUSP1. The results indicated that Lnc-FAM84B-4 regulates MAPK pathway by restraining DUSP1 expression. Mechanistically, RNA pull-down followed by mass spectrum determined hnRNPK functions as a binding partner of lnc-FAM84B-4 in mediating DUSP1 expression. Our findings demonstrate the important role of lnc-FAM84B-4-hnRNPK-DUSP1 axis in CRC development, and suggest a therapeutic target for CRC treatment.