ITPR3 Facilitates Tumor Growth, Metastasis and Stemness by Inducing the NF-ĸB/CD44 Pathway in Urinary Bladder Carcinoma

Zhang, Mengzhao; Wang, Lu; Yue, Yangyang; Zhang, Lu; Liu, Tianjie; Jing, Minxuan; Liang, Xiao; Ma, Minghai; Xu, Shan; Wang, Ke; Wang, Xinyang; Fan, Jinhai

doi:10.21203/rs.3.rs-135606/v1

Cited by 3 publications

(5 citation statements)

References 29 publications

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“…We found that migration ability was significantly suppressed in si-circIFT80 cells compared with si-NC cells, while on the migration capacity of CRC cells overexpressing circIFT80 was significantly higher than that of negative control cells (Figures 3(a) and 3(b)). MMP2 and MMP9, as the two most important members of the matrix metalloproteinases, play a crucial role in promoting cancer metastasis [14]. We found that the MMP2 and MMP9 protein levels were suppressed in HT-29 cells and SW480 cells after circIFT80 was knocked down.…”

Section: Circift80 Facilitated the Ability Of Crc Cells To Migratementioning

confidence: 79%

circIFT80 Functions as a ceRNA for miR-142, miR-568, and miR-634 and Promotes the Progression of Colorectal Cancer by Targeting β-Catenin

et al. 2022

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Colorectal cancer (CRC) is the third most common form of malignant tumor and is characterized by high rates of proliferation and metastases. Circular RNAs (circRNAs) are a form of noncoding and closed loop RNA molecules and play vital roles in the progression of various types of cancer in humans. Here, we used circRNA microarray sequencing technology to analyze the different circRNAs between CRC tissues and normal tissues and explore the role of circIFT80 in progression of colorectal cancer. In this present study, we found that circIFT80 was abnormally overexpression in colorectal cancer tissues and tumor cells. While knockout circIFT80 in HT29 cell or SW480 cells, the proliferation, and migration of the cells were inhibited, the cell cycle was arrested in G2/M phase, and the cell apoptosis was increased. And then, we found circIFT80-positive correlation with CTNNB1 (β-catenin) by sponging miR-142, miR-568, and miR-634 upregulated the gene expression. These miRNAs which targeted β-catenin mRNA were confirmed by dual-luciferase reporter system and RNA-pulldown. In addition, xenograft tumor experiments showed that circIFT80 accelerated the tumorigenesis of CRC in vivo. In conclusion, our work reveals the impacts of circIFT80 as ceRNA in the progression of CRC, by which sponging miR-142, miR-568, and miR-634 enhanced the expression levels of β-catenin and activation Wnt/β-catenin pathway. Collectively, our data indicate that circIFT80 serves as an oncogene in CRC and represents a novel candidate for diagnosis and treatment.

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Section: Circift80 Facilitated the Ability Of Crc Cells To Migratementioning

confidence: 79%

circIFT80 Functions as a ceRNA for miR-142, miR-568, and miR-634 and Promotes the Progression of Colorectal Cancer by Targeting β-Catenin

et al. 2022

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“…17 ITPR3 can also induce nuclear factor-kappa B/CD44 pathway signaling in urinary bladder carcinoma, thereby promoting tumor growth, stemlike behavior, and metastatic growth. 18 Increases in the expression of ITPR3 in hepatocellular carcinoma and colon cancer have also been linked to increased apoptotic activity and worse survival outcomes. 19,20 ITPR3 downregulation can suppress the migratory activity of breast cancer cells via oscillatory Ca 2+ signaling.…”

Section: Discussionmentioning

confidence: 99%

“…ITPR3 degradation in prostate cancer has been found to be associated with PTEN mutations, disrupting the ability of FBXL2 to bind to ITPR3 and thereby promote its degradation, thus suppressing mitochondrial Ca 2+ signaling within tumor cells, increasing their apoptotic sensitivity 17 . ITPR3 can also induce nuclear factor‐kappa B/CD44 pathway signaling in urinary bladder carcinoma, thereby promoting tumor growth, stem‐like behavior, and metastatic growth 18 . Increases in the expression of ITPR3 in hepatocellular carcinoma and colon cancer have also been linked to increased apoptotic activity and worse survival outcomes 19,20 .…”

Section: Discussionmentioning

confidence: 99%

“…Upon binding to IP3, ITPR3 mediates Ca 2+ release from the endoplasmic reticulum into the cytosol, leading to the activation of a series of Ca 2+ -dependent enzymes that can influence the proliferation, activation, differentiation, and apoptotic death of cells. [15][16][17][18] The overexpression of ITPR3 has been reported in breast cancer and several other malignancies, where it regulates the proliferative and invasive activity of tumor cells. [19][20][21] ITPR3 silencing can reduce breast cancer cell migration via Ca 2+ signature modulation.…”

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confidence: 99%

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Inositol 1,4,5‐trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population

Chen

Zhou

Jiang

et al. 2022

The Journal of Gene Medicine

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Background Mammalian inositol 1,4,5‐trisphosphate receptor (ITPR) genes encode ubiquitously expressed endoplasmic reticulum Ca2+ channels that have recently been shown to be closely linked to the pathogenesis of several cancers. However, few studies to date have explored associations between ITPR gene family single nucleotide polymorphisms (SNPs) and breast cancer risk. Methods In the present case–control study, 12 SNPs in the potential functional regions of the ITPR1, ITPR2, and ITPR3 genes were genotyped using an Illumina Infinium® Beadchip in 2095 Chinese women (1032 cases and 1063 controls). Results Multivariate logistic regression analyses indicated that a missense SNP in the ITPR3 coding region (rs2229642) was significantly related to breast cancer risk when using an additive model in this study (rs2229642‐adjusted odds ratio = 1.40, 95% confidence interval = 1.12–1.74, p = 2.97 × 10−3). Expression quantitative trait loci analyses indicated that the SNP rs2229642 was associated with reduced ITPR3 expression levels (p = 3.2 × 10−7) and with marked reductions in the expressions of several proximal genes, including BAK1, GRM4, HLA‐DOB, and UQCC2 (p = 0.013, 0.018, 3.4 × 10−3, 3.8 × 10−5), suggesting that it may further regulate other genes associated with oncogenic susceptibility. Kaplan–Meier analyses indicated that the patients with higher ITPR3 expression exhibited significantly poorer outcomes compared to the patients with lower expression of this gene (hazard ratio = 1.11, 95% confidence interval = 1–1.23, p = 0.046). Conclusions The results indicated that genetic variant in the coding region of ITPR3 gene may regulate the expressions of its host and some other cancer‐related genes, as well as act as potential predictive biomarker for susceptibility to breast cancer in the Chinese population.

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“…HKid-CRCC060PG-01) was purchased from Outdo Biotech Co., Ltd. (Shanghai, China) including 30 ccRCC tissues and corresponding adjacent noncancerous tissues. The tissue chip was subjected to the immunohistochemistry staining assay according to the protocol previously described in this research [22]. Especially, the primary antibody was purchased from Abcam (anti-GTSE1,1:500) (ab272670).…”

Section: Ccrcc Tissue Chip and Immunohistochemistry (Ihc) Assaysmentioning

confidence: 99%

High GTSE1 expression promotes cell proliferation, metastasis and cisplatin resistance in ccRCC and is associated with immune infiltrates and poor prognosis

Lei

Wang

2022

Preprint

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Background: Clear cell renal cell carcinoma (ccRCC) is the most common and fatal form of kidney cancer, accounting for 80% of new cases. Although it has been reported that GTSE1 is highly expressed in a variety of tumors and associated with malignant progression and poor clinical prognosis, its clinical significance, correlations with immune infiltration and biological function in ccRCC are still poorly understood.Methods: The gene expression, clinicopathological features, and clinical significance of GTSE1 were analyzed by multiple databases, including TCGA, GEO, TIMER, and UALCAN. Kaplan–Meier survival analysis; Gene set enrichment analysis (GSEA); Gene ontology enrichment (GO);Kyoto Encyclopedia of Genes and Genomes (KEGG); Tumor-infiltrating immune cells and immunomodulators were extracted and analyzed using TCGA ccRCC profiles. Protein-Protein interactions were built using the STRING website. The protein level of GTSE1 in ccRCC patients was detected by immunohistochemistry assay using the ccRCC tissue chip. Finally, MTT assay, colony formation assay, cell flow cytometry analysis, EdU staining assay, wound healing assay, transwell migration, and invasion assay were conducted to assess the biological function of GTSE1 in vitro. Results: GTSE1was overexpressed in ccRCC tissues and cells, and the overexpression of GTSE1 was associated with adverse clinical-pathological factors and poor clinical prognosis. Meanwhile, the functional enrichment analysis indicated that GTSE1 and its co-expressed genes were mainly related to the cell cycle, DNA replication, and immunoreaction such as T cell activation and innate immune response through multiple signaling pathways including the P53 signaling pathway and T cell receptor signaling pathway. Furthermore, we observed a significant relationship between the GTSE1 expression and immune infiltrating levels of different immune cells in ccRCC. Biological functional studies also demonstrated that GTSE1 could promote malignant progression of ccRCC by promoting cell proliferation, cell cycle transition, migration, invasion capacity, and decreasing the sensitivity of ccRCC cells to cisplatin. Conclusion: Our results indicate that GTSE1 serving as a potential oncogene that can promote the malignant progression and cisplatin resistance in ccRCC. Additionally, High GTSE1 expression contributes to an increased level of immune cell infiltration and is associated with a worse prognosis, providing a potential target for tumor therapy in ccRCC.

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ITPR3 Facilitates Tumor Growth, Metastasis and Stemness by Inducing the NF-ĸB/CD44 Pathway in Urinary Bladder Carcinoma

Cited by 3 publications

References 29 publications

circIFT80 Functions as a ceRNA for miR-142, miR-568, and miR-634 and Promotes the Progression of Colorectal Cancer by Targeting β-Catenin

circIFT80 Functions as a ceRNA for miR-142, miR-568, and miR-634 and Promotes the Progression of Colorectal Cancer by Targeting β-Catenin

Inositol 1,4,5‐trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population

High GTSE1 expression promotes cell proliferation, metastasis and cisplatin resistance in ccRCC and is associated with immune infiltrates and poor prognosis

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