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Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) modulates the proliferation and apoptosis of acute lymphoblastic leukemia cells by sponging miR-486-5p.

ABSTRACT: Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) is related to the progress of various cancers. Here, we illuminated the role of PVT1 in acute lymphoblastic leukemia (ALL) cell proliferation and apoptosis. PVT1 was upregulated in plasma samples from patients with ALL and ALL cell lines. PVT1 silencing repressed cell viability and enhanced cell apoptosis in Jurkat and SUP-B15 cells. PVT1 targeted microRNA-486-5p (miR-486-5p) and negatively modulated miR-486-5p expression. Upregulation of miR-486-5p decreased cell viability and increased ALL cell apoptosis. Mastermind Like Transcriptional Coactivator 3 (MAML3) was a downstream molecule of miR-486-5p and miR-486-5p mimic transfection weakened its expression in ALL cells. Rescue experiments proved that reintroduction of PVT1 counteracted the impacts of miR-486-5p in ALL cell proliferation and apoptosis. In vivo, PVT1 silencing repressed the tumor growth of SUP-B15 cells and reduced the expression of MAML3. Altogether, silencing of PVT1 inhibited ALL cell growth and induced cell apoptosis through sponging miR-486-5p.

SUBMITTER: Ju JK

PROVIDER: S-EPMC8973597 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) modulates the proliferation and apoptosis of acute lymphoblastic leukemia cells by sponging miR-486-5p.

Ju Jin-Ke JK Han Wei-Na WN Shi Cai-Ling CL

Bioengineered 20220201 2

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) is related to the progress of various cancers. Here, we illuminated the role of PVT1 in acute lymphoblastic leukemia (ALL) cell proliferation and apoptosis. PVT1 was upregulated in plasma samples from patients with ALL and ALL cell lines. PVT1 silencing repressed cell viability and enhanced cell apoptosis in Jurkat and SUP-B15 cells. PVT1 targeted microRNA-486-5p (miR-486-5p) and negatively modulated miR-486-5p express ...[more]

PMID: 35152842

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Project description:BackgroundLong-non-coding RNA PVT1 (lncRNA PVT1) can be used as an oncogenic regulatory non-coding RNA (ncRNA) for many cancers. However, its function and mechanism in breast cancer (BRCA) are still not clearly elucidated.ObjectiveWe attempt to explain the mechanism of PVT1's role in breast cancer from different perspectives.MethodsWe analyzed the expression of PVT1 and its correlation with the breast cancer related clinical data in the The Cancer Genome Atlas (TCGA) database. We used PVT1 overexpression and knockdown lentivirus to infect breast cancer MDA-MB-231 cell line for cell function verification, in vitro using CCK-8 to measure proliferation, flow cytometry to measure apoptosis, transwell test to measure invasion and migration ability, detecting cell extracellular acidification rate (ECAR) to assess glycolysis metabolism and explore the biological functions of PVT1 in breast cancer cells. Transcriptome sequencing was used to analyze the changes of related genes in cells after overexpression of PVT1. In vivo we used a xenograft model to study the effect of PVT1 on breast cancer.ResultsPVT1 was up-regulated in breast cancer tissues and was positively correlated with the clinical stage of breast cancer patients. Overexpression of PVT1 in vitro promoted cell proliferation, migration and invasion, and promoted tumor growth in vivo. Knockdown of PVT1 led to the opposite biological consequence. Further bioinformatics analysis showed that PVT1 changes the glycolysis metabolism of tumors through regulation of glycolysis-related genes. In addition, the expression of miR-145-5p is negatively correlated with PVT1. We consider the possibility of PVT1 promoting cell proliferation and metastasis by regulating the aerobic glucose metabolism in breast cancer cells through sponging the miR-145-5p.ConclusionOur results reveal a potential pathway for competing endogenous RNA to regulate breast cancer glucose metabolism. PVT1 regulates glycolysis related genes expression by competitively binding to endogenous miR-145-5p in breast cancer cells to change the metabolic phenotype. This may Provide new ideas for precise molecular therapy targets for breast cancer.

Dataset Information

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) modulates the proliferation and apoptosis of acute lymphoblastic leukemia cells by sponging miR-486-5p.

Publications

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) modulates the proliferation and apoptosis of acute lymphoblastic leukemia cells by sponging miR-486-5p.

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