Circ_0087851 suppresses colorectal cancer malignant progression through triggering miR-593-3p/BAP1-mediated ferroptosis.

Emerging research has validated that circular RNAs (circRNAs) have indispensable regulatory functions in tumorigenesis, including colorectal cancer (CRC). Ferroptosis is a specific cell death form and implicates in the malignant progression of tumors. Here, this study aimed to investigate the biofunction of circ_0087851 in tumor progression and ferroptosis of CRC, as well as its underlying molecular mechanism. The expression pattern of circ_0087851 in CRC was validated by qRT-PCR. The biological characteristics of circ_0087851 in CRC were assessed through CCK-8, colony formation and transwell assays in vitro. The ferroptosis was measured using ferroptosis-related reagents on iron, Fe2+, and lipid ROS detection. Bioinformatics, luciferase reporter, and RNA pulldown assays were employed to reveal the circ_0087851-mediated regulatory network. In addition, the effect of circ_0087851 on tumor growth in vivo was detected using a xenograft model. Circ_0087851 was notably diminished in CRC tissues and cells. Functionally, overexpression of circ_0087851 suppressed CRC cell growth, migration, invasion, and facilitated ferroptosis in vitro. Meanwhile, circ_0087851 upregulation impeded CRC growth in vivo. Mechanistically, circ_0087851 functioned as a molecular sponge for miR-593-3p, and BRCA1 associated protein 1 (BAP1) was identified as a downstream target of miR-593-3p. Besides, rescue experiments revealed that miR-593-3p overexpression or silencing of BAP1 reversed circ_0087851-mediated CRC progression. Circ_0087851 performed as a tumor suppressor and ferroptosis promoter by the miR-593-3p/BAP1 axis, providing novel biomarker and therapeutic target for the clinical management of CRC.

Huang M ，Gao T ，Chen X ，Yi J ，Zhou X ... -  《-》

Circ_0007142 downregulates miR-874-3p-mediated GDPD5 on colorectal cancer cells.

Ferroptosis is an iron-dependent and oxidative cell death form. Recent studies suggested that circular RNAs (circRNAs) regulated ferroptosis in tumour cells. Circ_0007142 was identified as a carcinogenic molecule in colorectal cancer (CRC), but its function on ferroptosis in CRC remains unknown. Circ_0007142, microRNA-874-3p (miR-874-3p) and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) levels were assayed using the quantitative real-time polymerase chain reaction (qRT-PCR). Cell survival and proliferation were measured by Cell Counting Kit-8 (CCK-8) assay. Protein detection was performed by Western blot. Cell apoptosis was analysed by flow cytometry. Ferroptosis was assessed by iron accumulation and oxidative stress. Target binding was evaluated by dual-luciferase reporter assay. In vivo research was conducted by tumour xenograft in mice. Circ_0007142 was overexpressed in CRC. After expression inhibition of circ_0007142, proliferation was reduced, while apoptosis and ferroptosis were facilitated in CRC cells. Mechanically, circ_0007142 was found as a miR-874-3p sponge and miR-874-3p inhibitor eliminated the regulation of si-circ_0007142 in CRC cells. MiR-874-3p targeted GDPD5 and upregulation of GDPD5 reversed the miR-874-3p-triggered tumour inhibition and ferroptosis promotion in CRC cells. Moreover, GDPD5 was regulated by the circ_0007142/miR-874-3p axis. Circ_0007142 also affected CRC tumorigenesis in vivo through the regulation of miR-874-3p and GDPD5. All these findings proved that circ_0007142/miR-874-3p/GDPD5 axis regulated tumorigenesis and ferroptosis of CRC cells. Circ_0007142 might be an available marker for ferroptosis in CRC therapy.

Wang Y ，Chen H ，Wei X 《-》

Circ_0087862 promotes tumorigenesis and glycolysis in colorectal cancer by sponging miR-296-3p to regulate PGK1 expression.

Circular RNAs (circRNAs) exert crucial roles in tumor progression of multiple cancers, including colorectal cancer (CRC). However, the functions of most circRNAs are not been fully elucidated. In this study, the role and mechanism of circ_0087862 in CRC were investigated. The expression of circ_0087862, microRNA-296-3p (miR-296-3p) and phosphoglycerate kinase 1 (PGK1) was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to assess cell proliferation. Flow cytometry was employed to analyze cell apoptosis. Transwell assay was employed to evaluate cell invasion. Western blot assay was employed to detect the level of related protein markers and PGK1. The glucose consumption, lactate production were tested by corresponding kits. The relationship between miR-296-3p and circ_0087862 or PGK1 was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. The in vivo function of circ_0087862 was examined by xenograft mice model. The expression levels of circ_0087862 and PGK1 were up-regulated in CRC tissues and cells, while miR-296-3p was down-regulated. Circ_0087862 silencing suppressed cell proliferation, invasion and glycolysis and promoted cell apoptosis in CRC cells. Circ_0087862 targeted miR-296-3p in CRC cells. MiR-296-3p inhibition reversed circ_0087862 silencing-mediated inhibition effect on cell proliferation, invasion and glycolysis, as well as the promotion effect on cell apoptosis. PGK1 was a target of miR-296-3p, and the overexpression of PGK1 attenuated miR-296-3p-mediated tumor suppression effect on CRC progression. Moreover, knockdown of circ_0087862 inhibited tumorigenesis in vivo. Circ_0087862 promoted CRC progression via miR-296-3p/PGK1 axis and might act as a potential target for CRC therapy.

Xiao W ，Li P 《-》

Circ-SMARCA5 suppresses colorectal cancer progression via downregulating miR-39-3p and upregulating ARID4B.

Circular RNAs are crucial in tumorigenesis. However, little is known about their functions in colorectal cancer (CRC). Circ-SMARCA5 was found to be an oncogene or tumor suppresser in different types of cancers, but its exact role in CRC remains unknown. Here, we aim to identify the role of circ-SMARCA5 in CRC development. Circ-SMARCA5 expression was determined by qRT-PCR. CRC cell proliferation, migration, and invasion were detected by CCK-8, wound healing, and Transwell assays, respectively. Bioinformatics analysis was performed to predict target genes. The interaction of microRNA (miR) with circ-SMARCA5 or target genes was detected using luciferase reporter assay. Xenograft model was established to determine the effect of circ-SMARCA5 on CRC tumor growth in vivo. Circ-SMARCA5 expression was dramatically decreased in CRC cell lines and tissues. Circ-SMARCA5 overexpression inhibited CRC cell proliferation, migration and invasion. MiR-93-3p was predicted as a target of circ-SMARCA5 and its overexpression attenuated the anti-tumor effect of circ-SMARCA5 on CRC cells. Furthermore, we predicted AT-rich interaction domain 4B (ARID4B) as the target of miR-39-3p. Functional analysis showed that circ-SMARCA5 upregulated ARID4B expression via miR-39-3p. Additionally, in vivo studies demonstrated that circ-SMARCA5 suppressed CRC tumor progression. Circ-SMARCA5 functions as a tumor suppressor by upregulating ARID4B expression via sponging miR-39-3p, and thereby inhibited CRC progression.

Miao X ，Xi Z ，Zhang Y ，Li Z ，Huang L ，Xin T ，Shen R ，Wang T ... -  《-》

Circ-ACAP2 facilitates the progression of colorectal cancer through mediating miR-143-3p/FZD4 axis.

Circular RNAs (circRNAs) play crucial roles in multiple cancers, including colorectal cancer (CRC). Here, we explored the role of circRNA ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 (circ-ACAP2) in the progression and radioresistance of CRC. Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were used to detect RNA and protein expression, respectively. The proliferation, apoptosis, migration, invasion and radioresistance of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, transwell migration assay, transwell invasion assay and colony formation assay. The target interaction between microRNA-143-3p (miR-143-3p) and circ-ACAP2 or frizzled class receptor 4 (FZD4) was verified by dual-luciferase reporter assay. Murine xenograft model was established to explore the role of circ-ACAP2 in vivo. The expression of circ-ACAP2 was prominently enhanced in CRC tissues and cell lines. Circ-ACAP2 facilitated the proliferation, migration, invasion and radioresistance whereas inhibited the apoptosis of CRC cells. MiR-143-3p was a direct target of circ-ACAP2 in CRC cells. Circ-ACAP2 promoted the progression and radioresistance of CRC partly by sponging miR-143-3p. MiR-143-3p interacted with the 3' untranslated region (3'UTR) of FZD4 in CRC cells, and FZD4 overexpression partly reversed miR-143-3p-mediated effects in CRC cells. Wnt/β-catenin signalling was modulated by circ-ACAP2/miR-143-3p/FZD4 axis in CRC cells. Circ-ACAP2 contributed to the development and radioresistance of CRC partly through targeting miR-143-3p/FZD4 axis, which provided novel potential diagnostic and therapeutic targets for CRC.

Zhang G ，Liu Z ，Zhong J ，Lin L ... -  《-》