GLUT and HK: Two primary and essential key players in tumor glycolysis.

Cancer cells reprogram their metabolism to become "glycolysis-dominant," which enables them to meet their energy and macromolecule needs and enhancing their rate of survival. This glycolytic-dominancy is known as the "Warburg effect", a significant factor in the growth and invasion of malignant tumors. Many studies confirmed that members of the GLUT family, specifically HK-II from the HK family play a pivotal role in the Warburg effect, and are closely associated with glucose transportation followed by glucose metabolism in cancer cells. Overexpression of GLUTs and HK-II correlates with aggressive tumor behaviour and tumor microenvironment making them attractive therapeutic targets. Several studies have proven that the regulation of GLUTs and HK-II expression improves the treatment outcome for various tumors. Therefore, small molecule inhibitors targeting GLUT and HK-II show promise in sensitizing cancer cells to treatment, either alone or in combination with existing therapies including chemotherapy, radiotherapy, immunotherapy, and photodynamic therapy. Despite existing therapies, viable methods to target the glycolysis of cancer cells are currently lacking to increase the effectiveness of cancer treatment. This review explores the current understanding of GLUT and HK-II in cancer metabolism, recent inhibitor developments, and strategies for future drug development, offering insights into improving cancer treatment efficacy.

Purinergic signaling promotes premature senescence.

Extracellular ATP activates P2 purinergic receptors. Whether purinergic signaling is functionally coupled to cellular senescence is largely unknown. We find that oxidative stress induced release of ATP and caused senescence in human lung fibroblasts. Inhibition of P2 receptors limited oxidative stress-induced senescence, while stimulation with exogenous ATP promoted premature senescence. Pharmacological inhibition of P2Y11 receptor (P2Y11R) inhibited premature senescence induced by either oxidative stress or ATP, while stimulation with a P2Y11R agonist was sufficient to induce cellular senescence. Our data show that both extracellular ATP and a P2Y11R agonist induced calcium (Ca++) release from the endoplasmic reticulum (ER) and that either inhibition of phospholipase C or intracellular Ca++ chelation impaired ATP-induced senescence. We also find that Ca++ that was released from the ER, following ATP-mediated activation of phospholipase C, entered mitochondria in a manner dependent on P2Y11R activation. Once in mitochondria, excessive Ca++ promoted the production of reactive oxygen species in a P2Y11R-dependent fashion, which drove development of premature senescence of lung fibroblasts. Finally, we show that conditioned medium derived from senescent lung fibroblasts, which were induced to senesce through the activation of ATP/P2Y11R-mediated signaling, promoted the proliferation of triple-negative breast cancer cells and their tumorigenic potential by secreting amphiregulin. Our study identifies the existence of a novel purinergic signaling pathway that links extracellular ATP to the development of a protumorigenic premature senescent phenotype in lung fibroblasts that is dependent on P2Y11R activation and ER-to-mitochondria calcium signaling.

Deciphering the interaction between PKM2 and the built-in thermodynamic properties of the glycolytic pathway in cancer cells.

Most cancer cells exhibit high glycolysis rates under conditions of abundant oxygen. Maintaining a stable glycolytic rate is critical for cancer cell growth as it ensures sufficient conversion of glucose carbons to energy, biosynthesis, and redox balance. Here we deciphered the interaction between PKM2 and the thermodynamic properties of the glycolytic pathway. Knocking down or knocking out PKM2 induced a thermodynamic equilibration in the glycolytic pathway, characterized by the reciprocal changes of the Gibbs free energy (ΔG) of the reactions catalyzed by PFK1 and PK, leading to a less exergonic PFK1-catalyzed reaction and a more exergonic PK-catalyzed reaction. The changes of the ΔGs of the two reactions causes the accumulation of intermediates, including the substrate PEP (the substrate of PK), in the segment between PFK1 and PK. The increased concentration of PEP in turn increased PK activity in the glycolytic pathway. Thus, the interaction between PKM2 and the thermodynamic properties of the glycolytic pathway maintains the reciprocal relationship between PK concentration and its substrate PEP concentration, by which, PK activity in the glycolytic pathway can be stabilized and effectively counteracts the effect of PKM2 KD or KO on glycolytic rate. In line with our previous reports, this study further validates the roles of the thermodynamics of the glycolytic pathway in stabilizing glycolysis in cancer cells. Deciphering the interaction between glycolytic enzymes and the thermodynamics of the glycolytic pathway will promote a better understanding of the flux control of glycolysis in cancer cells.

USP7 deubiquitinates epigenetic reader ZMYND8 to promote breast cancer cell migration and invasion.

The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinases (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.

A near-infrared fluorescent probe with a substantial Stokes shift designed for the detection and imaging of ß-galactosidase within living cells and animals.

ß-Galactosidase serves as a pivotal biomarker for both cancer and cellular aging. The advancement of fluorescent sensors for tracking ß-galactosidase activity is imperative in the realm of cancer diagnosis. We have designed a near-infrared fluorescent probe (PTA-gal) for the detection of ß-galactosidase in living systems with large Stokes shifts. PTA-gal exhibits remarkable sensitivity and selectivity in detecting ß-galactosidase, producing near-infrared fluorescent signals with a remarkably low detection limit (2.2 × 10-5 U/mL) and a high quantum yield (0.30). Moreover, PTA-gal demonstrates biocompatibility and can effectively detect ß-galactosidase in cancer cells as well as within living animals.

A progesterone derivative linked to a stable phospholipid activates breast cancer cell response without leaving the cell membrane.

In hormone-responsive breast cancer cells, progesterone (P4) has been shown to act via its nuclear receptor (nPR), a ligand-activated transcription factor. A small fraction of progesterone receptor is palmitoylated and anchored to the cell membrane (mbPR) forming a complex with estrogen receptor alpha (ERα). Upon hormone exposure, either directly or via interaction with ERα, mbPR activates the SRC/RAS/ERK kinase pathway leading to phosphorylation of nPR by ERK. Kinase activation is essential for P4 gene regulation, as the ERK and MSK1 kinases are recruited by the nPR to its genomic binding sites and trigger chromatin remodeling. An interesting open question is whether activation of mbPR can result in gene regulation in the absence of ligand binding to intracellular progesterone receptor (iPR). This matter has been investigated in the past using P4 attached to serum albumin, but the attachment is leaky and albumin can be endocytosed and degraded, liberating P4. Here, we propose a more stringent approach to address this issue by ensuring attachment of P4 to the cell membrane via covalent binding to a stable phospholipid. This strategy identifies the actions of P4 independent from hormone binding to iPR. We found that a membrane-attached progestin can activate mbPR, the ERK signaling pathway leading to iPR phosphorylation, initial gene regulation and entry into the cell cycle, in the absence of detectable intracellular progestin.

CircPHKB decreases the sensitivity of liver cancer cells to sorafenib via miR-1234-3p/CYP2W1 axis.

Sorafenib is currently the first-line treatment for patients with advanced liver cancer, but its therapeutic efficacy declines significantly after a few months of treatment. Therefore, it is of great importance to investigate the regulatory mechanisms of sorafenib sensitivity in liver cancer cells. In this study, we provided initial evidence demonstrating that circPHKB, a novel circRNA markedly overexpressed in sorafenib-treated liver cancer cells, attenuated the sensitivity of liver cancer cells to sorafenib. Mechanically, circPHKB sequestered miR-1234-3p, resulting in the up-regulation of cytochrome P450 family 2 subfamily W member 1 (CYP2W1), thereby reducing the killing effect of sorafenib on liver cancer cells. Moreover, knockdown of circPHKB sensitized liver cancer cells to sorafenib in vivo. The findings reveal a novel circPHKB/miR-1234-3p/CYP2W1 pathway that decreases the sensitivity of liver cancer cells to sorafenib, suggesting that circPHKB and the axis may serve as promising targets to improve the therapeutic efficacy of sorafenib against liver cancer.

Genomic and transcriptomic characteristics of 12 novel primary cell lines derived from three patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive bile duct malignancy with poor prognosis. To improve our understanding of the biological characteristics of CCA and develop effective therapies, appropriate preclinical models are required. Here, we established and characterized 12 novel patient-derived primary cancer cell (PDPC) models using multi-region sampling. At the genomic level of PDPCs, we observed not only commonly mutated genes, such as TP53, JAK3, and KMT2C, consistent with the reports in CCA, but also specific mutation patterns in each cell line. In addition, specific expression patterns with distinct biological functions and pathways involved were also observed in the PDPCs at the transcriptomic level. Furthermore, the drug-sensitivity results revealed that the PDPCs exhibited different responses to the six commonly used compounds. Our findings indicate that the established PDPCs can serve as novel in vitro reliable models to provide a crucial molecular basis for improving the understanding of tumorigenesis and its treatment.

The effect of baseline O2 conditions on the response of prostate cancer cells to hypoxia.

The transcriptional response to hypoxia is largely regulated by the hypoxia-inducible factors (HIFs), which induce the expression of genes involved in glycolysis, angiogenesis, proliferation, and migration. Virtually all cell culture-based hypoxia experiments have used near-atmospheric (18% O2) oxygen levels as the baseline for comparison with hypoxia. However, this is hyperoxic compared with mammalian tissue microenvironments, where oxygen levels range from 2% to 9% O2 (physioxia). Thus, these experiments actually compare hyperoxia to hypoxia. To determine how the baseline O2 level affects the subsequent response to hypoxia, we cultured PC-3 prostate cancer cells in either 18% or 5% O2 for 2 wk before exposing them to hypoxia (∼1.1% pericellular O2) for 12-48 h. RNA-seq revealed that the transcriptional response to hypoxia was dependent on the baseline O2 level. Cells grown in 18% O2 before hypoxia exposure showed an enhanced induction of HIF targets, particularly genes involved in glucose metabolism, compared with cells grown in physioxia before hypoxia. Consistent with this, hypoxia significantly increased glucose consumption and metabolic activity only in cells previously cultured in 18% O2, but not in cells preadapted to 5% O2. Transcriptomic analyses also indicated effects on cell proliferation and motility, which were followed up by functional assays. Although unaffected by hypoxia, both proliferation and migration rates were greater in cells cultured in 5% O2 versus 18% O2. We conclude that an inappropriately hyperoxic starting condition affects the transcriptional and metabolic responses of PC-3 cells to hypoxia, which may compromise experiments on cancer metabolism in vitro.NEW & NOTEWORTHY Although human cell culture models have been instrumental to our understanding of the mechanisms involved in the cellular response to hypoxia, in virtually all experiments, cells are routinely cultured in near-atmospheric (∼18% O2) oxygen levels, which are hyperoxic relative to physiological conditions in vivo. Here, we show for the first time that cells cultured in physiological O2 levels (5% O2) respond differently to subsequent hypoxia than cells grown at 18%.

Blockage of aquaporin-3 peroxiporin activity by organogold compounds affects melanoma cell adhesion, proliferation and migration.

Aquaporin-3 (AQP3) is a membrane channel with dual aquaglyceroporin/peroxiporin activity, facilitating the diffusion of water, glycerol and H2O2 across cell membranes. AQP3 shows aberrant expression in melanoma and its role in cell adhesion, migration and proliferation is well described. Gold compounds were shown to modulate AQP3 activity with reduced associated toxicity, making them promising molecules for cancer therapy. In this study, we validated the phenotype resulting from AQP3-silencing of two melanoma cell lines, MNT-1 and A375, which resulted in decreased H2O2 permeability. Subsequently, the AQP3 inhibitory effect of a new series of organogold compounds derived from Auphen, a potent AQP3 inhibitor, was first evaluated in red blood cells (RBCs) that highly express AQP3, and then in HEK-293T cells with AQP3 overexpression to ascertain the compounds' specificity. The first screening in RBCs unveiled two organogold compounds as promising blockers of AQP3 permeability. Moderate reduction of glycerol permeability but drastic inhibition of H2O2 permeability was detected for some of the gold derivatives in both AQP3-overexpressing cells and human melanoma cell lines. Additionally, all compounds were effective in impairing cell adhesion, proliferation and migration, although in a cell type-dependent manner. In conclusion, our data show that AQP3 peroxiporin activity is crucial for melanoma progression and highlight organogold compounds as promising AQP3 inhibitors with implications in melanoma cell adhesion, proliferation and migration, unveiling their potential as anticancer drugs against AQP3-overexpressing tumours. KEY POINTS: AQP3 affects cellular redox balance. Gold compounds inhibit AQP3 permeability in melanoma cells. AQP3 is involved in cell adhesion, proliferation and migration of melanoma. Blockage of AQP3 peroxiporin activity impairs melanoma cell migration. Gold compounds are potential anticancer drug leads for AQP3-overexpressing cancers.

Fibroblast growth factor homologous factors: canonical and non-canonical mechanisms of action.

Since their discovery nearly 30 years ago, fibroblast growth factor homologous factors (FHFs) are now known to control the functionality of excitable tissues through a range of mechanisms. Nervous and cardiac system dysfunctions are caused by loss- or gain-of-function mutations in FHF genes. The best understood 'canonical' targets for FHF action are voltage-gated sodium channels, and recent studies have expanded the repertoire of ways that FHFs modulate sodium channel gating. Additional 'non-canonical' functions of FHFs in excitable and non-excitable cells, including cancer cells, have been reported over the past dozen years. This review summarizes and evaluates reported canonical and non-canonical FHF functions.

HMGB1 prefers to interact with structural RNAs and regulates rRNA methylation modification and translation in HeLa cells.

BACKGROUND: High-mobility group B1 (HMGB1) is both a DNA binding nuclear factor modulating transcription and a crucial cytokine that mediates the response to both infectious and noninfectious inflammation such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. HMGB1 has been proposed to control ribosome biogenesis, similar as the other members of a class of HMGB proteins. RESULTS: Here, we report that HMGB1 selectively promotes transcription of genes involved in the regulation of transcription, osteoclast differentiation and apoptotic process. Improved RNA immunoprecipitation by UV cross-linking and deep sequencing (iRIP-seq) experiment revealed that HMGB1 selectively bound to mRNAs functioning not only in signal transduction and gene expression, but also in axon guidance, focal adhesion, and extracellular matrix organization. Importantly, HMGB1-bound reads were strongly enriched in specific structured RNAs, including the domain II of 28S rRNA, H/ACA box snoRNAs including snoRNA63 and scaRNAs. RTL-P experiment showed that overexpression of HMGB1 led to a decreased methylation modification of 28S rRNA at position Am2388, Cm2409, and Gm2411. We further showed that HMGB1 overexpression increased ribosome RNA expression levels and enhanced protein synthesis. CONCLUSION: Taken together, our results support a model in which HMGB1 binds to multiple RNA species in human cancer cells, which could at least partially contribute to HMGB1-modulated rRNA modification, protein synthesis function of ribosomes, and differential gene expression including rRNA genes. These findings provide additional mechanistic clues to HMGB1 functions in cancers and cell differentiation.

Construction of a Synergy Combination Model for Turmeric (Curcuma longa L.) and Black Pepper (Piper nigrum L.) Extracts: Enhanced Anticancer Activity against A549 and NCI-H292 Human Lung Cancer Cells.

Extensive research on medicinal herbs for bioactive compounds proposes that they could replace synthetic drugs, reducing side effects and economic burdens. Especially, interest in the synergistic benefits of natural products is increasing, implying that their combined use may enhance therapeutic effectiveness. This study aimed to explore the synergetic effects of turmeric (Curcuma longa L.) and black pepper (Piper nigrum L.) extract on lung normal (MRC-5) and cancer (A549 and NCI-H292) cell lines. The turmeric extract (TM) only affected the lung cancer cell lines, but it had no impact on the MRC-5 cell line. On the other hand, the black pepper extract (BP) did not cause any damage to either the lung normal or cancer cell lines, even at concentrations of up to 400 µg/mL. Response surface methodology was used to predict the ideal synergistic concentrations (EC50) of TM and BP, which were found to be 48.5 and 241.7 µg/mL, respectively. Notably, the selected condition resulted in higher cytotoxicity compared to the exposure to TM alone, indicating a potent synergetic effect. The rate of curcumin degradation under this combined treatment was significantly decreased to 49.72 ± 5.00 nmol/h/µg for A549 cells and 47.53 ± 4.78 nmol/h/µg for NCI-H292 cells, respectively, as compared to curcumin alone. Taken together, this study confirmed the potent synergistic effect of TM and BP on lung cancer cell lines. Further research is required to identify their specific synergetic mechanisms. Our findings provide crucial foundational data on the synergistic effects of TM and BP.

Changing the Landscape of Solid Tumor Therapy from Apoptosis-Promoting to Apoptosis-Inhibiting Strategies.

The many limitations of implementing anticancer strategies under the term "precision oncology" have been extensively discussed. While some authors propose promising future directions, others are less optimistic and use phrases such as illusion, hype, and false hypotheses. The reality is revealed by practicing clinicians and cancer patients in various online publications, one of which has stated that "in the quest for the next cancer cure, few researchers bother to look back at the graveyard of failed medicines to figure out what went wrong". The message is clear: Novel therapeutic strategies with catchy names (e.g., synthetic "lethality") have not fulfilled their promises despite decades of extensive research and clinical trials. The main purpose of this review is to discuss key challenges in solid tumor therapy that surprisingly continue to be overlooked by the Nomenclature Committee on Cell Death (NCCD) and numerous other authors. These challenges include: The impact of chemotherapy-induced genome chaos (e.g., multinucleation) on resistance and relapse, oncogenic function of caspase 3, cancer cell anastasis (recovery from late stages of apoptosis), and pitfalls of ubiquitously used preclinical chemosensitivity assays (e.g., cell "viability" and tumor growth delay studies in live animals) that score such pro-survival responses as "lethal" events. The studies outlined herein underscore the need for new directions in the management of solid tumors.

RING1 Inhibition Has a Cell-Specific Antitumoral Role by Promoting Autophagy in Endometrial Cancer Cells.

BACKGROUND/AIMS: Factors influencing gene expression through chemical modifications of histones may play an important role in the regulation of the autophagy process in cancers. RING1A or RING1B are responsible for the catalytical activity of Polycomb repressive complex 1 (PRC1) which monoubiquitylate histone H2A. The aim of the study was to determine the effect of the RING1A/B protein inhibition on the autophagy process in endometrial cancer cells and the anticancer effectiveness of RING1 inhibitor PRT4165 in combination with autophagy inhibitors. METHODS: The expression of autophagy genes and proteins were analyzed in endometrial cancer cells HEC-1A and Ishikawa grown in different glucose concentrations and treated with PRT4165. To assess the effectiveness of PRT4165 used alone or in combination with HCQ or Lys05, IC50 and the combination index (CI) were calculated. Flow cytometry method was used to estimate apoptotic cells after treatment. RESULTS: The results confirm the impact of RINGs on autophagy and apoptosis in endometrial cancer cells. PRT4165 inhibitor causes changes in the expression of ATG genes and autophagy markers and the effect depends on glucose concentration and cell types. However, the anticancer effectiveness of PRT4165 was lower when it was used in combination with autophagy inhibitors, suggesting that such a combination is not a promising anticancer strategy. CONCLUSION: The results indicate the importance of the RINGs in the process of autophagy and apoptosis. Further potentially more effective combinations of PRT4165 with autophagy modulators should be sought.

FFAR-mediated signaling drives migration of pancreatic cancer cells in hypoxic fibroblast co-cultures.

The tumor microenvironment (TME) comprises cancer and non-cancerous stromal cells, including fibroblasts. Free fatty acids (FFAs) regulate various biological responses by binding to G protein-coupled FFA receptors (FFARs). In this study, we examined the impact of FFAR1 and FFAR4 on the cell migration of pancreatic cancer PANC-1 cells co-cultured with 3T3 fibroblast cells under hypoxic conditions. PANC-1 cells cultured at 1 % O2 exhibited elevated FFAR1 expression and decreased FFAR4 expression compared to those at 21 % O2. Cell migration of PANC-1 cells was reduced under 1 % O2 conditions. FFAR1 knockdown enhanced PANC-1 cell migration, whereas FFAR4 knockdown inhibited it. Co-culture of PANC-1 cells with 3T3 cells at 1 % O2 significantly increased FFAR4 expression, while FFAR1 expression remained unchanged. To evaluate the effects of FFAR1 and FFAR4 on PANC-1 cell migration in co-culture with 3T3 cells, we conducted a wound healing assay using the Culture-Insert 2 Well. PANC-1 and 3T3 cells were individually seeded into the two wells and incubated at both 21 % and 1 % O2 for 13 h. The cell migration of PANC-1 cells co-cultured with 3T3 cells at 1 % O2 was notably higher compared to 21 % O2. TUG-770 reduced and TUG-891 enhanced the cell migration of PANC-1 cells co-cultured with 3T3 cells under both 21 % and 1 % O2 conditions. These findings suggest that FFAR1 and FFAR4 play important roles in regulating the cell migration of PANC-1 cells co-cultured with 3T3 cells under hypoxic conditions.

Modeling Absorption Dynamics of Differently Shaped Gold Glioblastoma and Colon Cells Based on Refractive Index Distribution in Holotomographic Imaging.

Herein, it is demonstrated that the toxic effect of gold nanoparticles (Au NPs) on three different cancer cell lines (U-118 and LN-299 glioblastoma and HCT-116 colon) depends on their absorption dynamics by cells, related to the shapes of the NPs. This hypothesis is confirmed by showing that i) based on refractive index (RI) values, typical for cell components and gold nanoparticles, it is possible to show the absorption dynamics and accumulation locations of the latter ones inside and outside of the cells. Moreover, ii) the saturation of the accumulated Au NPs volume in the cells depends on the nanoparticle shape and is reached in the shortest time for star-shaped Au NPs (AuS NPs) and in the longest time for spherical Au NPs (AuSph NPs) and on the cancer cells, where the longest and the shortest saturation are noticed for HCT-116 and LN-229 cells, respectively. A physical model of Au NPs absorption dynamics is proposed, where the diameter and shape of the Au NPs are used as parameters. The obtained theoretical data are consistent with experimental data in 85-98%.

MiR-3680-3p is a novel biomarker for the diagnosis and prognosis of liver cancer and is involved in regulating the progression of liver cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that can actively participate in post-transcriptional regulation of genes. A number of studies have shown that miRNAs can serve as important regulators of cancer cell growth, differentiation, and apoptosis. They can also act as markers for the diagnosis and prognosis of certain cancers. To explore the potential prognosis-related miRNAs in liver cancer patients, to provide theoretical basis for early diagnosis and prognosis of liver cancer, as well as to provide a new direction for the targeted therapy of liver cancer. The miRNA expression profiles of liver cancer patients in the the Cancer Genome Atlas database were comprehensively analyzed and various prognostic-related miRNAs of liver cancer were screened out. The data was further subjected to survival analysis, prognostic analysis, gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis, microenvironment analysis, and drug sensitivity analysis by R Language version 4.2.0. Finally, the screened miRNAs were further validated by different experiments. Thus, miNRAs involved in liver cancer diagnosis and prognosis were identified. MiRNA-3680-3p was found to be significantly different in 10 different cancers, including liver cancer, and was significantly associated with the microenvironment, survival, and prognosis of liver cancer patients. In addition, drug sensitivity analysis revealed that miRNA-3680-3p can provide a useful reference for drug selection in targeted therapy for liver cancer. MiRNA-3680-3p can serve as a biomarker for the diagnosis and prognosis of liver cancer patients and down-regulation of miRNA-3680-3p could significantly inhibit both the proliferation and migration of liver cancer cells.

Research progress of ZIC5 for tumor metastasis.

The zinc finger protein of the cerebellum (ZIC) family comprises five members (ZIC1-5), homologous with the odd-paired (OPA) gene in Drosophila melanogila. These transcription factors contain five Cys2His zinc finger domains, constituting one of the most abundant transcription factor families in human cells. ZIC proteins significantly contribute to transcriptional regulation and chromatin remodeling. As a member of the ZIC family, ZIC5 is essential for animal growth and development. Numerous studies have investigated the connection between ZIC proteins and cancer as well as tumor metastases in recent years. Many studies have found that within tumor tissues, the transcription and translation processes increase the expression of ZIC5 which is linked to tumor aggressiveness. This review aims to provide an objective summary of the impact of ZIC5 on tumor metastasis and consider the potential application of ZIC5 targets in both tumor therapy and the early detection of cancer.

Roles of lysophosphatidic acid (LPA) receptor-mediated signaling in cancer cell biology.

Lysophosphatidic acid (LPA) is a simple lipid which is endogenously synthesized from lysophosphatidylcholine (LPC) by autotaxin (ATX). LPA mediates a variety of cellular responses through the binding of G protein-coupled LPA receptors (LPA1 to LPA6). It is considered that LPA receptor-mediated signaling plays an important role in the pathogenesis of human malignancy. Genetic alterations and epigenetic changes of LPA receptors have been detected in some cancer cells as well as LPA per se. Moreover, LPA receptors contribute to the promotion of tumor progression, including cell proliferation, invasion, metastasis, tumorigenicity, and angiogenesis. In recent studies, the activation of LPA receptor-mediated signaling regulates chemoresistance and radiosensitivity in cancer cells. This review provides an updated overview on the roles of LPA receptor-mediated signaling in the regulation of cancer cell functions and its potential utility as a molecular target for novel therapies in clinical cancer approaches.