Circular RNA hsa_circ_0004277 contributes to malignant phenotype of colorectal cancer by sponging miR‐512‐5p to upregulate the expression of PTMA

Abstract

In recent years, extensive reports have been published concerning the molecular mechanism underlying the occurrence and progression of colorectal cancer. Circular RNAs (circRNAs) have been identified as important modulators in the biological processes of colorectal cancer. Microarray analysis unveiled that differential circ‐0004277 expression was identified in tissue samples of colorectal cancer. High circ‐0004277 expression was then verified in tissue samples and cell lines of colorectal cancer via qRT‐PCR. Kaplan–Meier analysis was used for identifying the association between circ‐0004277 expression and the overall survival rate of colorectal cancer patients. A relationship existed between higher circ‐0004277 expression and decreased overall survival rate of colorectal cancer patients. From a functional perspective, circ‐0004277 knockdown accelerated cell apoptosis and restrained cell proliferation of colorectal cancer. From mechanistic perspective, circ‐0004277 upregulated PTMA by sponging miR‐512‐5p. Rescue assay was used for verifying the roles of the circ‐0004277‐miR‐512‐5p‐PTMA axis. Both miR‐512‐5p and PTMA participated in circ‐0004277‐mediated colorectal cancer cell proliferation based on experiments. In summary, our study showed that circ‐0004277 promoted the proliferation of colorectal cancer cells as a miR‐512‐5p sponge to upregulate the PTMA expression.

The role of XBP-1-mediated unfolded protein response in colorectal cancer progression-a regulatory mechanism associated with lncRNA-miRNA-mRNA network

“…1 ). Interestingly, except miR-500a-3p, the other 3 miRNAs have been reported to inhibit the malignant phenotype of tumors [ 18 – 20 ]. Then, further upstream analysis was conducted and SLFNL1-AS1, KCNQ1OT1, NEAT1, XIST, AC016876.2 and AC026362.1 were lncRNAs that could bind to the above 4 miRNAs and be degraded.…”

lncRNA cytoskeleton regulator reduces non‑small cell lung cancer radiosensitivity by downregulating miRNA‑206 and activating prothymosin α

“…Subsequently, the present study indicated that, as a target of miR-206, PTMA overexpression debilitated the inhibitory role of CYTOR depletion in NSCLC cell radiosensitivity, as evidenced by the improved Ki67-positive rate. As a downstream factor in the ceRNA network, the upregulation of PTMA caused the outgrowth of exacerbated colorectal cancer ( 61 ). Furthermore, PTMA exhibited a negative association with the radiosensitivity of colorectal cancer ( 41 ).…”

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

“…Hsa_circ_0004277 promotes the proliferation of colorectal cancer cells, acting as a miR-512-5p sponge to upregulate the expression of an oncogene PTMA (Prothymosin alpha) in CRC [ 135 ]. The overexpressed PTMA induces the proteasome degradation of tumor suppressor p53 (wild type) through ubiquitination by Mdm2 (E3 ubiquitin-protein ligase), and thus PTMA is free to exert its oncogenic functions.…”

“…Bcl-2 and Bax are also significantly changed by circCSNK1G1 (hsa_circ_101555, hsa_circ_0001955) [ 183 ]. Silencing of hsa_circ_0004277 significantly increases caspase-3 activity [ 135 ]. CircABCB10 (hsa_circ_0008717) negatively regulate miR-326 and upregulates CCL5 (Chemokine (C-C motif) ligand 5) to suppress cell ferroptosis and apoptosis [ 198 ].…”