Erratum: miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells: Erratum.

[This corrects the article DOI: 10.7150/jca.42731.].

miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells.

Purpose: MicroRNAs (miRNAs) are key regulators of the growth and development of a wide range of cancer types such as colorectal cancer (CRC). A number of previously studies have observed that the levels of miR-365a-3p expression are dysregulated in many cancers, but the specific role of this miRNA in CRC and its association with patient prognosis remains unclear. Methods: The expression of miR-365a-3p in CRC tissues and cell lines was detected by Real-time Quantitative polymerase chain reaction (RT-qPCR), while the relationship between miR-365a-3p expression and clinicopathological characteristics was further analyzed. After increasing the expression of miR-365a-3p by plasmid transfection in CRC cells, we further investigated the cell proliferation, invasion and migration by cell counting kit-8 (CCK-8), and Transwell assays. Epithelial-mesenchymal transition (EMT) pathway was also measured by western blotting. In addition, the relationship among miR-365a-3p, ADAM10 and JAK in CRC, was explored by luciferase reporter assay. Results: In the present study, we determined that CRC cells and clinical samples exhibited decreased miR-365a-3p expression, and this was associated with larger tumor size, lymph node metastasis, and local invasion. Patients with lower expression of miR-365a-3p had significantly decreased recurrence-free survival (RFS) and overall survival (OS) relative to those with higher levels of this miRNA. In a multivariate analysis, we confirmed that reduced miR-365a-3p levels were independently predictive of poorer CRC patient outcomes. In a functional study, we determined that elevated miR-365a-3p expression inhibited the ability of CRC cells to proliferate and metastasize in vitro and in vivo. We further identified ADAM10 as a direct miR-365a-3p target, resulting in the suppression of ADAM10 expression in cells expressing this miRNA and ADAM10 levels were in turn closely linked to JAK/STAT signaling. Conclusion: Our study suggested the ability of miR-365a-3p to inhibit the progression of CRC at least in part via suppressing ADAM10 expression and associated JAK/STAT signaling, thus identifying this signaling axis as a possible prognostic and therapeutic target in CRC.

The RNA binding protein neuro-oncological ventral antigen 1 (NOVA1) regulates IL-6 mRNA stability to enhance JAK2-STAT3 signaling in CRC.

The molecular mechanisms governing the metastasis of colorectal cancer (CRC) are incompletely understood. In the present study, we found NOVA1 to be expressed at higher levels in CRC cell lines and tissue samples, and this upregulation was positively correlated with TNM stage (p = 0.034), poor differentiation (p = 0.001), and lymph node metastasis (p = 0.008). Both overall survival (OS) and relapse-free survival (RFS) were both significantly decreased in patients with high NOVA1 expression relative to those with low expression. Through a multivariate analysis, we determined that NOVA1 independently predicted poor outcomes in those with CRC. In further functional studies, we found that NOVA1 expression controlled the proliferation and invasive characteristics of CRC cells via a mechanism wherein NOVA1 bound and stabilized the IL6 mRNA, enhancing IL-6/JAK2/STAT3 signaling to in turn upregulate matrix metalloproteinases (MMPs) 2, 7, and 9. NOVA1 therefore plays key functional roles in regulating CRC progression, and our results further indicate that it serve as a valuable prognostic biomarker and potentially a target for therapeutic treatment in individuals with CRC.