miR-424 targets AKT3 and PSAT1 and has a tumor-suppressive role in human colorectal cancer

Abstract

BackgroundRecent advances in cancer biology have uncovered critical roles for microRNAs in regulating tumor responses. This study is to elucidate the role of miR-424 in colorectal cancer development.Materials and methodsmiR-424 expression was analyzed by qRT-PCR. The role of miR-424 was studied in cell lines and animal models. The downstream targets of miR-424 were determined by microarray analysis.ResultsWe found that miR-424 expression was downregulated in human colorectal cancer cell lines and patient biopsies. We demonstrated that miR-424 functioned as a tumor suppressor by suppressing colorectal cancer growth in vitro and in vivo and enhancing apoptosis. Using microarray screening, we subsequently presented evidence that miR-424 directly targeted the 3′ untranslated regions of the AKT serine/threonine kinase 3 (AKT3) and phosphoserine aminotransferase 1 (PSAT1) mRNAs via luciferase assay. Furthermore, AKT3 or PSAT1 silencing partially recapitulated the effects of miR-424.ConclusionThis newly identified miR-424/AKT3–SAT1 axis may represent a novel therapeutic strategy for future treatment of colorectal cancer.

Overexpression of PSAT1 Gene is a Favorable Prognostic Marker in Lower-Grade Gliomas and Predicts a Favorable Outcome in Patients with IDH1 Mutations and Chromosome 1p19q Codeletion

“…An underlying mechanism that explains how overexpression of the PSAT1 gene contributes to a favorable outcome in LGG patients remains unclear. A number of studies have suggested overexpression of PSAT1 protein as a poor prognostic marker in colorectal cancer [17], esophageal squamous cell carcinoma [15], NSCLC [14] and ER(−) breast cancer [16]. However, a recent study suggested that a high level of PSAT1 protein could be a favorable prognostic marker for regorafenib-induced GBM suppression [18].…”

“…Overexpression of PSPH was found in hepatocellular cancer [12] and colorectal cancer [13]. PSAT1 mediates carbon metabolism and the TCA cycle, which provides energy and increases biomass in non-small cell lung cancer (NSCLC) [14], breast cancer [16] and colorectal cancer [17]. However, the prognostic roles of these three genes in LGGs are still unknown.…”

“…PSAT1 is a pivotal enzyme that governs the production of two metabolites, serine and α-ketoglutarate (α-KG), which are involved in one carbon metabolism and the TCA cycle, respectively. PSAT1 was regarded as a poor prognostic marker in non-small cell lung cancer [14], esophageal squamous cell carcinoma [15], breast cancer [16] and colorectal cancer [17] and contributes to cancer cell proliferation and metastasis. In contrast, maintenance of PSAT1 protein at a high level has been identified as a marker for a favorable outcome in GBM with regorafenib treatment [18].…”

Peer Review #2 of "A six-microRNA signature can better predict overall survival of patients with esophagus adenocarcinoma (v0.1)"

“…Hsa-mir-424 was recognized to play a dual role in various cancers. In colorectal cancer, hsa-mir-424 was identified as a tumor suppressor by suppressing cancer cell growth and enhancing apoptosis (Fang et al 2018). In addition, hsa-mir-424 was upregulated and correlated with poor survival in esophageal squamous cell carcinoma, it can promote cell proliferation by multilayered regulation of cell cycle (Wen et al 2018).…”

<p>Role of miRNA-424 in Cancers</p>

“…miR-424-5p is a carcinogen in colorectal cancer (CRC) that directly promotes proliferation and metastasis by targeting SCN4B, CCNE1, AKT3, and Rictor. [45][46][47][48] In the field of hepatobiliary carcinoma, it has been found that miR-424-5p can inhibit the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5. Moreover, in liver cancer, miR-424 can inhibit the proliferation and invasion of tumors by targeting TRIM29, YAP1, and c-Myb, while miR-424-5p can also target ICAT and inhibit tumor progression by reversing the EMT process of primary liver cancer.…”