GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC

Abstract

BackgroundTNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC.MethodsWe analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis.ResultsIn the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC.ConclusionsThese results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC.

Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor–based combination therapy

“…Bulk high‐throughput RNA sequencing identified several immune activation‐related genes as the top DEGs. GLDC was upregulated in the HPV+ group and has been reported to exert a potential anticancer effect by activating CD4 + T cells in triple‐negative breast cancer (TNBC) 23 . CYP4F12, another upregulated gene, may positively correlate with immune cell infiltration by CD8 + T cells and M1 macrophages 24 .…”

Transcriptome Profiling Based at Different Time Points after Hatching Deepened Our Understanding on Larval Growth and Development of Amphioctopus fangsiao

“…GLDC, a key enzyme in the glycine cleavage system, is involved in glycine metabolism and the conversion of glycine into a one-carbon unit, thereby enhancing glucose metabolism, energy metabolism, and other metabolic processes [ 18 , 19 , 20 ]. Prior research demonstrates that elevated expression of GLDC boosts cell proliferation, reinforces cell antioxidant capacity, improves cell survival, and significantly expedites the development of an organism’s tissues and organs [ 21 , 22 , 23 ].…”

Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer

“…Tumor glycolysis produces a large amount of lactate, which inhibits the infiltration and activity of immune cells (e.g., CD8+ T cells and NK cells) and may lead to tumor immune escape 14 . Recently, HX et al suggested that GLDC has a potential role in regulating cell proliferation and tumor immune infiltration in triple-negative breast cancer (TNBC) 15 . This evidence suggested that GLDC might affect immune cell infiltration or tumor immune escape by mediating tumor glycolysis, and its roles in prostate cancer need to be further confirmed.…”