Dataset Information

LncRNA MANCR positively affects the malignant progression of lung adenocarcinoma.

ABSTRACT:

Background

LncRNA MANCR (mitosis-related lncRNA, LINC00704) is deemed as a pivotal regulator in various cancers, yet the biological function it performs in lung adenocarcinoma (LUAD) was rarely reported. We made an in-depth study to clarify its effect during the progression of this cancer.

Methods

Expression data and clinical information were first accessed from TCGA LUAD dataset ( https://portal.gdc.cancer.gov/repository ). Differentially expressed lncRNAs were identified. R package "survival" determined the survival significance of the lncRNA MANCR. GSEA software was applied to conduct single sample enrichment analysis. qRT-PCR was used to examine MANCR expression. The expression levels of related proteins were tested using Western blot assay. The impact of MANCR on cancer cell biological behaviors was investigated via cell function experiments.

Results

MANCR was significantly upregulated in LUAD cells. It also resulted in a poor prognosis. When MANCR expression was down-regulated, the expression of proteins related to invasion and migration, cell cycle and proliferation was decreased, while the expression of proteins associated with apoptosis was elevated. Furthermore, in vitro experiments revealed that silencing MANCR inhibited cancer cell functions, blocked cell cycle progression while promoting cell apoptosis.

Conclusion

LncRNA MANCR can lead to enhanced proliferative, invasive and migratory abilities of cancer cells while reducing cell apoptosis. Hence, MANCR might be a novel biomarker of LUAD.

SUBMITTER: Liu C

PROVIDER: S-EPMC8379881 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLong non-coding RNAs (lncRNAs) have become potential therapeutic targets or promising prognostic biomarkers in cancers. However, individual gene does not show sufficient prognostic value for clear cell renal cell carcinoma (ccRCC). Therefore, this study aims to develop a combined prognostic lncRNA signature to the prognosis of ccRCC.MethodsThe transcriptome profiling data for confirmed ccRCC cases were obtained from The Cancer Genome Atlas (TCGA; https://portal.gdc.cancer.gov/). The prognostic significance, survival time and diagnostic effectiveness of the lncRNAs in ccRCC was evaluated using Kaplan-Meier method, the log-rank test and receiver operating characteristic (ROC) curves, respectively. The area under the ROC curve (AUC) of the 4 lncRNAs was also performed. The expression of mitotically-associated lncRNA (MANCR) was measured in ccRCC cells or tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Both Colony formation assays and Cell Counting Kit-8 (CCK-8) assay was conducted to detect the proliferation of both 786-O and SN12C cells. For apoptosis detection, flow cytometry in both 786-O and SN12C cells was performed. For migration of 786-O and SN12C cells detection, wound healing and transwell assays were performed.ResultsA total of 1,567 differentially expressed lncRNAs in ccRCC were discerned with 1,340 upregulation and 227 downregulation. Furthermore, a 4-lncRNA signature (FIRRE, MANCR, AC103706.1, and AC018648.1) model was obtained that showed good performance in the prognosis of ccRCC. Gene Ontology (GO) analysis showed that these protein-coding genes (PCGs) were mainly enriched in ATPase activity, catalytic activity, and acting on RNA protein serine/threonine kinase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that PCGs were mainly involved in endocytosis, oocyte meiosis and spliceosome. In addition, we revealed that MANCR was highly expressed in ccRCC cells and tissues and downregulation of MANCR inhibited cell proliferation and migration. In contrast, apoptosis of 786-O and SN12C cells was promoted with MANCR suppression.ConclusionsA 4-lncRNA prognostic model that presented good performance for prognosis of ccRCC patients was established. Knockdown of MANCR inhibited cell proliferation and migration, and promoted apoptosis of 786-O and SN12C cells, suggesting that a 4-lncRNA signature model might be an essential for ccRCC prognosis.