Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma

Abstract

Background Inositol Polyphosphate-5-Phosphatase B (INPP5B), a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD. Methods TCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan–Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein–protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein–protein interactions. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays. Result INPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway. Conclusion Our results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People’s Hospital. The Ethics Committee of Hangzhou First People’s Hospital has approved this study. (registration number: IIT-20210907-0031-01; registration date: 2021.09.13)

Single-Cell Transcriptomic Analysis Reveals Macrophage–Tumor Crosstalk in Hepatocellular Carcinoma

“…To validate the expression of selected genes between tumoradjacent tissues and HCC tissues, HCC patient's gene expression data (fragments per kilobase of transcript per million mapped reads (FPKM) processed, n = 421, including 50 normal tissues and 371 HCC tissues) from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database (https:// xenabrowser.net/datapages/) and the Human Protein Atlas (HPA) database (https://www.proteinatlas.org/, for protein expression) (22) were used in our study.…”

Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer

“…6 B-b). The decreased expression of INPP5B is associated with poor prognosis in lung adenocarcinoma [ 62 ]. The loss of PAK3, one of the serine/threonine kinase family members, prevents cancer cell growth in the absence of p53 [ 63 ].…”

Identification of immune regulatory protein coding genes in the development of lung adenocarcinom a (LUAD)

“…Recently, some novel biomarkers have been identified for LUAD. For example, low expression of RS1 or inositol polyphosphate-5-phosphatase b (INPP5B) might be a potential independent prognostic indicator for LUAD [6]. Higher CDC25C expression was upregulated in LUAD, which could accelerate malignant progression of LUAD, and restrained efficacy nivolumab in LUAD treatment [7].…”