Epigenetic frontiers: miRNAs, long non-coding RNAs and nanomaterials are pioneering to cancer therapy DOI Creative Commons
Rajkumar Prabhakaran,

Rajkumar Thamarai,

Sivabalan Sivasamy

и другие.

Epigenetics & Chromatin, Год журнала: 2024, Номер 17(1)

Опубликована: Окт. 16, 2024

Cancer has arisen from both genetic mutations and epigenetic changes, making epigenetics a crucial area of research for innovative cancer prevention treatment strategies. This dual perspective propelled into the forefront research. review highlights important roles DNA methylation, histone modifications non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) long RNAs, which are key regulators cancer-related gene expression. It explores potential epigenetic-based therapies to revolutionize patient outcomes by selectively modulating specific markers involved in tumorigenesis. The examines promising biomarkers early detection prognosis. also recent progress oligonucleotide-based therapies, including antisense oligonucleotides (ASOs) antimiRs, precisely modulate processes. Furthermore, concept editing is discussed, providing insight future role precision medicine patients. integration nanomedicine therapy been explored offers approaches improve therapeutic efficacy. comprehensive advances seeks advance field oncology, ultimately culminating improved fight against cancer.

Язык: Английский

Lactate‐induced protein lactylation: A bridge between epigenetics and metabolic reprogramming in cancer DOI Creative Commons
Ting Wang, Ye Zeng, Zheng Li

и другие.

Cell Proliferation, Год журнала: 2023, Номер 56(10)

Опубликована: Апрель 14, 2023

Lactate is not only an endpoint of glycolysis but gradually being discovered to play the role a universal metabolic fuel for energy via 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours fast-growing has made lactate pivotal player reprogramming, which enables obtain abundant short time. Moreover, can provide favourable conditions tumorigenesis by shaping acidic tumour microenvironment, recruiting immune cells, etc. recently lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms production, circulation utilization. As with other epigenetic modifications, modify histone proteins alter spatial configuration chromatin, affect DNA accessibility regulate expression corresponding genes. What's more, degree inseparable from spatialized concentration, builds bridge epigenetics reprogramming. Here, we review important summarize latest finding try explore therapeutic strategies oncotherapy that kill two birds one stone.

Язык: Английский

Процитировано

77
VEGF signaling: Role in angiogenesis and beyond DOI
Pallab Shaw, Shailendra Kumar Dhar Dwivedi, Resham Bhattacharya

и другие.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(2), С. 189079 - 189079

Опубликована: Янв. 26, 2024

Язык: Английский

Процитировано

58
HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription DOI Creative Commons

Ziping Niu,

Chen Chen, Siyu Wang

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 26, 2024

Lysine lactylation (Kla) links metabolism and gene regulation plays a key role in multiple biological processes. However, the regulatory mechanism functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as lysine lactyltransferase regulate transcription. We show catalyzes addition vitro intracellularly, E508 is site for activity HBO1. Quantitative proteomic analysis further reveals 95 endogenous sites targeted by HBO1, with majority located on histones. Using site-specific antibodies, find may preferentially catalyze histone H3K9la scaffold proteins including JADE1 BRPF2 can promote enzymatic Kla. Notably, CUT&Tag assays demonstrate required transcription start (TSSs). Besides, regulated signaling pathways tumorigenesis, which supported evaluating malignant behaviors HBO1- knockout (KO) tumor cells, well level clinical tissues. Our study serves mediate Kla-dependent

Язык: Английский

Процитировано

44
Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2‐Mediated MLH1 Intron Retention DOI Creative Commons
Yue Qu,

Zhao Wang,

Yixiong Shen

и другие.

Advanced Science, Год журнала: 2024, Номер 11(19)

Опубликована: Март 13, 2024

Abstract Temozolomide (TMZ) resistance remains the major obstacle in treatment of glioblastoma (GBM). Lactylation is a novel post‐translational modification that involved various tumors. However, whether lactylation plays role GBM TMZ unclear. Here it found histone H3K9 (H3K9la) confers via LUC7L2‐mediated intron 7 retention MLH1. Mechanistically, upregulated recurrent tissues and TMZ‐resistant cells, mainly concentrated H3K9. Combined multi‐omics analysis, including CUT&Tag, SLAM‐seq, RNA‐seq, reveals significantly enriched LUC7L2 promoter activates transcription to promote its expression. mediates MLH1 reduce expression, thereby inhibit mismatch repair (MMR), ultimately leading resistance. Of note, identified clinical anti‐epileptic drug, stiripentol, which can cross blood–brain barrier lactate dehydrogenase A/B (LDHA/B) activity, acts as inhibitor renders cells more sensitive vitro vivo. These findings not only shed light on mechanism but also provide potential combined therapeutic strategy for treatment.

Язык: Английский

Процитировано

41
Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD DOI Creative Commons
Yang Long,

Kunwei Niu,

Jianlin Wang

и другие.

Journal of Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Апрель 1, 2024

Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack detailed understanding oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. role protein lactylation, newly unraveled post-translational modification that orchestrates expression, remains largely elusive in pathogenesis iCCA.

Язык: Английский

Процитировано

30
Lactate and lactylation: Behind the development of tumors DOI

Enci Dai,

Wei Wang, Yingying Li

и другие.

Cancer Letters, Год журнала: 2024, Номер 591, С. 216896 - 216896

Опубликована: Апрель 17, 2024

Язык: Английский

Процитировано

26
Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription DOI Creative Commons
Yu Zhang, Hang Song, Meili Li

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(3)

Опубликована: Март 1, 2024

Abstract Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T‐cell dysfunction. The lactate‐induced lactylation of histone lysine residues is noteworthy, it functions an epigenetic modification that directly augments gene transcription from chromatin. This originating effectively fosters a reliance on transcription, thereby expediting tumour progression development. Herein, this review explores the correlation between characteristics, revealing innovative process enhances vulnerability malignancy. Moreover, imperative acknowledge paramount importance acknowledging therapeutic methodologies for proficiently managing by precisely targeting signalling. comprehensive illuminates crucial yet inadequately investigated aspect lactylation, providing valuable insights into its clinical ramifications prospective interventions centred lactylation.

Язык: Английский

Процитировано

17
Lactate and lactylation in cancer DOI Creative Commons
Jie Chen, Ziyue Huang,

Ya Chen

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 11, 2025

Abstract Accumulated evidence has implicated the diverse and substantial influence of lactate on cellular differentiation fate regulation in physiological pathological settings, particularly intricate conditions such as cancer. Specifically, been demonstrated to be pivotal molding tumor microenvironment (TME) through its effects different cell populations. Within cells, impacts signaling pathways, augments shuttle process, boosts resistance oxidative stress, contributes lactylation. In various populations, interplay between immune cells governs processes differentiation, response, surveillance, treatment effectiveness. Furthermore, communication stromal/endothelial supports basal membrane (BM) remodeling, epithelial-mesenchymal transitions (EMT), metabolic reprogramming, angiogenesis, drug resistance. Focusing production transport, specifically dehydrogenase (LDH) monocarboxylate transporters (MCT), shown promise Inhibitors targeting LDH MCT act both suppressors enhancers immunotherapy, leading a synergistic therapeutic effect when combined with immunotherapy. The review underscores importance progression provides valuable perspectives potential approaches that target vulnerability metabolism, highlighting Heel Achilles for cancer treatment.

Язык: Английский

Процитировано

9
CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1 DOI Creative Commons
Jingyu Liao, Zeyu Chen,

Ruizhi Chang

и другие.

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(16), С. 5218 - 5232

Опубликована: Янв. 1, 2023

The centromere proteins (CENPs), a critical mitosis-related protein complexes, are involved in the kinetochore assembly and chromosome segregation. In this study, we identified that CENPA was significantly up-regulated HCC highly expressed correlated with poor prognosis for patients. Knockdown of inhibited cell proliferation tumor growth vitro vivo. Mechanistically, transcriptionally activated cooperated YY1 to drive expression cyclin D1 (CCND1) neuropilin 2 (NRP2). Moreover, can be lactylated at lysine 124 (K124). lactylation K124 promotes activation, leading enhanced its target genes. summary, function as transcriptional regulator promote via cooperating YY1. Targeting CENPA-YY1-CCND1/NRP2 axis may provide candidate therapeutic targets HCC.

Язык: Английский

Процитировано

32
Histone lactylation regulates cancer progression by reshaping the tumor microenvironment DOI Creative Commons
Junxing Qu, Peizhi Li, Zhiheng Sun

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 27, 2023

As a major product of glycolysis and vital signaling molecule, many studies have reported the key role lactate in tumor progression cell fate determination. Lactylation is newly discovered post-translational modification induced by lactate. On one hand, lactylation introduced new era metabolism microenvironment (TME), on other it provided breakthrough point for elucidation interaction between metabolic reprogramming epigenetic modification. Studies shown that cells, stem cells tumor-infiltrating immune TME can participate development cancer through downstream transcriptional regulation, potential promising treatment target. This review summarized discovery effects lactylation, as well recent research histone regulating reshaping TME. We also focused strategies to enhance anti-tumor via targeting lactylation. Finally, we discussed limitations existing proposed perspectives future order further explore targets. It may provide way direction improve prognosis.

Язык: Английский

Процитировано

27