Activation of IGF/IGF-IR signaling pathway fails to induce epithelial-mesenchymal transition in pancreatic cancer cells

Kopantzev, E. P.; Kopantseva, M. R.; Grankina, E. V.; Mikaelyan, Arsen; Егоров, В. Н.

doi:10.1016/j.pan.2019.01.010

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…The Group ABGI is the most expressed, whereas the Group CDE, which is composed by potential coding transcript variants, is almost undetectable in most cell lines ( Figure 3A). Interestingly, in pancreatic tumors the highest expression of HMGA2-AS1 transcripts was found in PANC1 cell line, which is considered more aggressive than BX-PC3 (43)(44)(45). Similarly, we observed a higher expression of HMGA2-AS1 transcripts in prostatic cancer cell line PC3 with respect to DU145 cell line ( Figure 3A).…”

Section: Hmga2-as1 Transcript Variants Are Expressed In Cancer Cell Lsupporting

confidence: 56%

HMGA2 Antisense Long Non-coding RNAs as New Players in the Regulation of HMGA2 Expression and Pancreatic Cancer Promotion

et al. 2020

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Background: Natural antisense long non-coding RNAs (lncRNAs) are regulatory RNAs transcribed from the opposite strand of either protein coding or non-coding genes, able to modulate their own sense gene expression. Hence, their dysregulation can lead to pathologic processes. Cancer is a complex class of diseases determined by the aberrant expression of a variety of factors, among them, the oncofetal chromatin architectural proteins High Mobility Group A (HMGA) modulate several cancer hallmarks. Thus, we decided to investigate the presence of natural antisense lncRNAs in HMGA1 and HMGA2 loci, and their possible involvement in gene expression regulation. Methods: We used FANTOM5 data resources, FANTOM-CAT genome browser and Zenbu visualization tool, which employ 1,829 human CAGE and RNA-sequencing libraries, to determine expression, ontology enrichment, and dynamic regulation of natural antisense lncRNAs in HMGA1 and HMGA2 loci. We then performed qRT-PCR in different cancer cell lines to validate the existence of HMGA2-AS1 transcripts. We depleted HMGA2-AS1 transcripts with siRNAs and investigated HMGA2 expression by qRT-PCR and western blot analyses. Moreover, we evaluated cell viability and migration by MTS and transwell assays, and EMT markers by qRT-PCR and immunofluorescence. Furthermore, we used bioinformatics approaches to evaluate HMGA2 and HMGA2-AS1 correlation and overall survival in tumor patients. Results: We found the presence of a promoter-associated lncRNA (CATG00000088127.1) in the HMGA1 gene and three antisense genes (RPSAP52, HMGA2-AS1, and RP11-366L20.3) in the HMGA2 gene. We studied the uncharacterized HMGA2-AS1 transcripts, validating their existence in cancer cell lines and observing a positive correlation between HMGA2 and HMGA2-AS1 expression in a cancer-derived patient dataset. We showed that HMGA2-AS1 transcripts positively modulate HMGA2 expression and migration properties of PANC1 cells through HMGA2. In addition, Kaplan-Meier analysis showed that high level of HMGA2-AS1 is a negative prognostic factor in pancreatic cancer patients. Ros et al. HMGA2 Regulation by HMGA2-AS1 Conclusions: Our results describe novel antisense lncRNAs associated with HMGA1 and HMGA2 genes. In particular, we demonstrate that HMGA2-AS1 is involved in the regulation of its own sense gene expression, mediating tumorigenesis. Thus, we highlight a new layer of complexity in the regulation of HMGA2 expression, providing new potential targets for cancer therapy.

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Section: Hmga2-as1 Transcript Variants Are Expressed In Cancer Cell Lsupporting

confidence: 56%

HMGA2 Antisense Long Non-coding RNAs as New Players in the Regulation of HMGA2 Expression and Pancreatic Cancer Promotion

et al. 2020

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“…We first analyzed the expression of Arid5a in commercially available human pancreatic cancer cell lines retaining epithelial and quasi-mesenchymal (QM) characteristics (27,28).…”

Section: Arid5a Promotes Immune Evasion By Pancreatic Cancermentioning

confidence: 99%

Arid5a Promotes Immune Evasion by Augmenting Tryptophan Metabolism and Chemokine Expression

Parajuli

Tekgüç

Wing

et al. 2021

Cancer Immunology Research

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“…The upregulated expression of IGF-1 also predicted a poor clinical outcome in patients with PC. Moreover, the IGF-1 receptor (IGF-1R) was revealed to have tyrosine kinase activity (30). Upon IGF-1R binding with IGF-1, the receptor is activated and increases the phosphorylation levels of AKT and MEK proteins, leading to the activation of intracellular signaling pathways, such as the PI3K/Akt/mTOR pathway and RAS/RAF/MEK/ERK signaling pathway (31).…”

Section: Discussionmentioning

confidence: 99%

miRNA‑7515 suppresses pancreatic cancer cell proliferation, migration and invasion via downregulating IGF‑1 expression

Lei

Zeng

et al. 2021

Oncol Rep

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Pancreatic cancer (PC) is a lethal malignancy of the gastrointestinal tract. Previous studies have reported that microRNAs (miRNAs/miRs) are involved in the tumorigenesis of PC. Therefore, the present study aimed to determine the effects of miR-7515 on PC cell proliferation, invasion and migration in vitro and in vivo, and investigate its underlying molecular mechanism using bioinformatics, double luciferase assay and western blotting. The results revealed that the expression levels of miR-7515 were downregulated in PC, which predicted a poor clinical outcome. The overexpression of miR-7515 significantly decreased the proliferation, invasive and migratory abilities of PC cells in vitro and in vivo, while the knockdown of miR-7515 exerted the opposite effects.

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Activation of IGF/IGF-IR signaling pathway fails to induce epithelial-mesenchymal transition in pancreatic cancer cells

Cited by 10 publications

References 24 publications

HMGA2 Antisense Long Non-coding RNAs as New Players in the Regulation of HMGA2 Expression and Pancreatic Cancer Promotion

HMGA2 Antisense Long Non-coding RNAs as New Players in the Regulation of HMGA2 Expression and Pancreatic Cancer Promotion

Arid5a Promotes Immune Evasion by Augmenting Tryptophan Metabolism and Chemokine Expression

miRNA‑7515 suppresses pancreatic cancer cell proliferation, migration and invasion via downregulating IGF‑1 expression

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