Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer

Peng, Chao-Zhong; Li, Xiao; Ye, Zhixue; Wu, Wenqing

doi:10.1038/s41598-021-95798-7

Cited by 4 publications

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RAB1A belongs to the Rab1 protein isoform in the Rab protein family, which is an essential vesicle transporter between the endoplasmic reticulum and Golgi apparatus [ 31 ]. In cancer development, abnormal expression of RAB1A is involved in the progression of various cancers, such as colon cancer [ 32 ], tongue cancer [ 33 ], and glioma [ 34 ] in humans, all of which exhibit some degree of cancer-promoting effects in a gene dose-dependent manner. More notably, the promoting effect of RAB1A on malignant hepatocytes in HCC has also long been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Exosome-transmitted circ_002136 promotes hepatocellular carcinoma progression by miR-19a-3p/RAB1A pathway

et al. 2022

View full text Add to dashboard Cite

Background Circular RNAs (circRNAs) are enriched in exosomes and are extremely stable. Exosome-mediated intercellular transfer of specific biologically active circRNA molecules can drive the transformation of the tumor microenvironment and accelerate or inhibit the local spread and multifocal growth of hepatocellular carcinoma (HCC). In this study, we explored in depth about the biological roles of HCC cell-derived exosomes and exosome-transported circRNAs on HCC in vivo and in vitro. Methods Exosomes extracted from HCC cells (Huh7 and HA22T) were characterized using transmission electron microscopy, nanoparticle size tracer analysis, and western blotting. Exosomes were observed for endocytosis using fluorescent labeling. The effects of HCC cell-derived exosomes and the circ_002136 they carried on cell growth, metastasis and apoptosis were determined by CCK-8 assay, transwell assay, flow cytometry analysis and TUNEL staining, respectively. The expressions of circ_002136, miR-19a-3p and RAB1A were detected by quantitative RT-PCR (qRT-PCR). Targeted binding between miR-19a-3p and circ_002136 or RAB1A was predicted and verified by bioinformatics analysis, dual-luciferase reporter and RNA pull-down experiments. The in vivo effect of circ_002136 was determined by constructing a xenograft tumor model. Results The findings revealed that Huh7 and HA22T exosomes conferred enhanced viability as well as invasive ability to recipient HCC cells. Circ_002136 was shown for the first time to be differentially upregulated in HCC tissues and cells and transferred by HCC cell-derived exosomes. More importantly, selective silencing of circ_002136 depleted the malignant biological behaviors of HCC exosome-activated Huh7 and HA22T cells. Depletion of circ_002136 in vivo effectively retarded the growth of HCC xenograft tumors. Furthermore, a well-established circ_002136 ceRNA regulatory network was constructed, namely circ_002136 blocked miR-19a-3p expression, elevated RAB1A expression activity and stimulated HCC development. Finally, high levels of circ_002136 or RAB1A, as well as low levels of miR-19a-3p, negatively affected HCC patient survival. Conclusion The study on circ_002136 provides good data to support our insight into the mechanism of to-be-silenced circRNA as a therapeutic agent in the progression of HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Exosome-transmitted circ_002136 promotes hepatocellular carcinoma progression by miR-19a-3p/RAB1A pathway

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The latter is a small GTPase, which is involved in vesicular trafficking between the endoplasmic reticulum and the Golgi apparatus (194). RAB1A was shown to mediate proliferation and migration of colorectal cancer (195). 4) was down-regulated in EOC tissues and cell lines (196).…”

Section: Circrnas Targeting Ras Pathway-related Proteinsmentioning

confidence: 99%

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in PreclinicalIn VivoModels: Identification of Targets and New Modalities for Therapeutic Intervention

WEIDLE,

BIRZELE

2024

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) is associatedwith a dismal prognosis due to development of resistance to chemotherapy and metastasis in the peritoneal cavity and distant organs. In order to identify new targets and treatment modalities we searched the literature for up-and and downregulated circRNAs with efficacy in preclinical EOC-related in vivo systems. Our search yielded circRNAs falling into the following categories: cisplatin and paclitaxel resistance, transmembrane receptors, secreted factors, transcription factors, RNA splicing and processing factors, RAS pathwayrelated components, proteolysis and cell-cycle regulation, signaling-related proteins, and circRNAs regulating proteins in additional categories. These findings can be potentially translated by validation and manipulation of the corresponding targets, inhibition of circRNAs with antisense oligonucleotides (ASO), small interfering RNAs (siRNA) or small hairpin RNA (shRNA) or by reconstituting their activity.The incidence of ovarian cancer (OC) in the USA is 22,000 cases per year and 14,000 deaths, and 29,000 deaths in Europe (1). The vast majority are epithelial ovarian cancers (EOC). This type of tumor is typically treated with a combination of surgery and chemotherapy, which often includes cisplatin (DDP) and paclitaxel (PTX). An exciting development was the treatment of homologous recombination-deficient ovarian tumors with breast cancer antigen (BRCA) mutations or deletions with poly-ADP-ribose polymerase (PARP) inhibitors (2). Three PARP inhibitors (olaparib, rucaparib and niraparib) have been approved for the treatment of OCs in different clinical settings. In addition, anti-angiogenic therapy with Bevacizumab was approved (3). Nevertheless, recurrence due to resistance mechanisms is commonly observed and significantly impairs the therapeutic benefit of treatment (4). Epithelial ovarian cancer (EOC) gains a growth advantage due to interactions with fat cells, mesothelial cells, and cancerassociated fibroblasts. These interactions enhance the activation of pathways that support its growth (5-7). Also, its dissemination in ascites fluid and formation of nodules in the peritoneum are a unique mechanism of metastasis hampering therapeutic intervention (8, 9). Immunotherapy with checkpoint inhibitors such as Pembrolizumab has shown limited success (10). Diverse mechanisms of immune escape in a tumorlocation specific manner have been observed (11). Taken together, there is a tremendous medical need for identification of new targets and modalities for treatment of OC. Therefore, we searched the literature for circular RNAs (circRNAs) that are up-or down-regulated in EOC and upon their modulation exhibit efficacy in preclinical in vivo models of EOC. Circular RNA in CancercircRNA can be generated during mRNA processing by intramolecular mRNA pairing followed by circularization, RNA-213

show abstract

Ubiquitin–proteasome system as a target for anticancer treatment—an update

et al. 2023

View full text Add to dashboard Cite

Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer

Cited by 4 publications

References 30 publications

Exosome-transmitted circ_002136 promotes hepatocellular carcinoma progression by miR-19a-3p/RAB1A pathway

Exosome-transmitted circ_002136 promotes hepatocellular carcinoma progression by miR-19a-3p/RAB1A pathway

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in PreclinicalIn VivoModels: Identification of Targets and New Modalities for Therapeutic Intervention

Ubiquitin–proteasome system as a target for anticancer treatment—an update

Contact Info

Product

Resources

About