<p><em>AKAP12</em> Endogenous Transcripts Suppress The Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Directly Targeting oncomiR-183-5p</p>

Abstract

PurposeRestoring lost function to suppressor gene products has captured the interest of the research community in the field of gene therapy. AKAP12, also known as Gravin/AKAP250, is a tumor suppressor gene, and its deregulation may be responsible for cancer progression. The aim of this study was to investigate whether AKAP12 mRNA has an anti-cancer function by regulating onco-miRNA expression in colorectal cancer (CRC) cells.MethodsmiRNAs targeting AKAP12 were predicted by bioinformatics analysis and further confirmed by dual-luciferase reporter assays and RT-qPCR. The altered expression of microRNA was validated in early-stage CRC tumor tissues by miRseq. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) assay. Cell invasion and migration were detected by transwell and wound healing assays, respectively. In vivo experiments were conducted to confirm the in vitro findings.ResultsAmong all miRNAs, reversed correlation between AKAP12 expression and miRNA-183-5p expression was most significant. Luciferase assays revealed that AKAP12 directly targeted miR-183-5p. The miRseq data showed that miR-183 was also dysregulated at the early stage of tumor development and upregulated in late sub-stage II CRC patients (P<0.01). Mechanistic analysis both in vitro and in vivo demonstrated that anti-miR-183-5p depressed cell proliferation, migration, and invasion in CRC cells while miR-183-5p overexpression resulted in opposite effects.ConclusionOur findings suggested that oncomiR-183-5p promoted the proliferation, migration, and invasion of CRC cells. AKAP12 miRNA-binding elements (MREs) suppressed miRNA-183-5p activities. Any change in expression of AKAP12 thus affected miRNA-183-5p. This may be another anti-tumor mechanism in addition to protein-mediation that regulates tumor suppressor genes.

Dual Oxidase 2 (DUOX2) as a Proteomic Biomarker for Predicting Treatment Response to Chemoradiation Therapy for Locally Advanced Rectal Cancer: Using High-Throughput Proteomic Analysis and Machine Learning Algorithm

“…A further two-group analysis between CR and nCR also demonstrated the overexpression of proteins that play a tumor-suppressive role, including AKAP12 [ 15 ], DCTN3 [ 16 ], and SELENOH [ 17 ], in the CR group ( Figure 2 ). In the nCR group, several key proteins were upregulated, including DUOX2 [ 18 , 19 ], PQCTL [ 20 ], DIAPH1 [ 21 ], SUPT5H [ 22 ], and MUC13 [ 23 ], which promote cell migration and invasiveness (DIAPH1, SUPT5H, and MUC13), immune surveillance escape (QPCTL), and epithelial–mesenchymal transition (EMT; DUOX2) ( Figure 2 ).…”

Loss of coordinated expression between ribosomal and mitochondrial genes revealed by comprehensive characterization of a large family with a rare mendelian disorder

“…TMEM158 is a Ras induced senescence protein which is involved in proliferation arrest and its overexpression is linked to ovarian cancer [17]. Cyclin dependent kinase 11a ( CDK11A ), is a serine/threonine-protein kinase that controls cell cycle [18], and AKAP12 is a tumor suppressor, inhibitor of cell migration and regulates cell-cycle progression through Src-mediated oncogenic signaling and cytoskeletal pathways [19,20]. An individual in this family with mild DBA symptoms was diagnosed with breast cancer at age 36, and there is an increased observed incidence of neoplasia including breast in the DBA registry.…”

“…AKAP12 is a tumor suppressor, inhibitor of cell migration and regulates cell-cycle progression through Src-mediated oncogenic signaling and cytoskeletal pathways [19,20]. An individual in this family with mild DBA symptoms was diagnosed with breast cancer at age 36, and there is an increased observed incidence of neoplasia including breast in the DBA registry.…”

MiR-183-5p Promotes the Cell Proliferation of Colorectal Cancer by Targeting QKI-5

“…The role of miR-183-5p in CRC has also received some attention. Research by Hu et al showed that AKAP12 endogenous transcripts inhibited the proliferation, migration and invasion of CRC cells by targeting miR-183-5P [21]. Research by Zheng et al pointed out that miR-183-5P enhances the radioresistance of CRC by directly targeting ATG5 [22].…”