The Prognostic Value and Regulatory Mechanisms of microRNA-145 in Various Tumors: A Systematic Review and Meta-analysis of 50 Studies

Abstract

Acting as an important tumor-related miRNA, the clinical significance and underlying mechanisms of miR-145 in various malignant tumors have been investigated by numerous studies. This study aimed to comprehensively estimate the prognostic value and systematically illustrate the regulatory mechanisms of miR-145 based on all eligible literature.Relevant studies were acquired from multiple online databases. Overall survival (OS) and progression-free survival (PFS) were used as primary endpoints. Detailed subgroup analyses were performed to decrease the heterogeneity among studies and recognize the prognostic value of miR-145. All statistical analyses were performed with RevMan software version 5.3 and STATA software version 14.1. A total of 48 articles containing 50 studies were included in the meta-analysis. For OS, the pooled results showed that low miR-145 expression in tumor tissues was significantly associated with worse OS in patients with various tumors [HR ¼ 1.70; 95% confidence interval (CI), 1.46-1.99; P < 0.001). Subgroup analysis based on tumor type showed that the downregulation of miR-145 was associated with unfavorable OS in colorectal cancer (HR ¼ 2.17; 95% CI, 1.52-3.08; P < 0.001), ovarian cancer (HR ¼ 2.15; 95% CI, 1.29-3.59; P ¼ 0.003), gastric cancer (HR ¼ 1.78; 95% CI, 1.35-2.36; P < 0.001), glioma (HR ¼ 1.65; 95% CI, 1.30-2.10; P < 0.001), and osteosarcoma (HR ¼ 2.28; 95% CI, 1.50-3.47; P < 0.001). For PFS, the pooled results also showed that the downregulation of miR-145 was significantly associated with poor PFS in patients with multiple tumors (HR ¼ 1.39; 95% CI, 1.16-1.67; P < 0.001), and the subgroup analyses further identified that the low miR-145 expression was associated with worse PFS in patients with lung cancer (HR ¼ 1.97; 95% CI, 1.25-3.09; P ¼ 0.003) and those of Asian descent (HR ¼ 1.50; 95% CI, 1.23-1.82; P < 0.001). For the regulatory mechanisms, we observed that numerous tumor-related transcripts could be targeted by miR-145-5p or miR-145-3p, as well as the expression and function of miR-145-5p could be regulated by multiple molecules.This meta-analysis indicated that downregulated miR-145 in tumor tissues or peripheral blood predicted unfavorable prognostic outcomes for patients suffering from various malignant tumors. In addition, miR-145 was involved in multiple tumor-related pathways and the functioning of significant biological effects. miR-145 is a well-demonstrated tumor suppressor, and its expression level is significantly correlated with the prognosis of patients with multiple malignant tumors.

NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells

“…In colon and breast cancer cells, miR-145 reduces the levels of several oncoproteins, such as c-MYC and VEGF [ 35 , 36 ], decreasing cell proliferation and the angiogenic potential of cancer cells. In EOC, miR-145 was proposed as a diagnosis marker and predictor of disease outcome [ 37 , 38 ]. In addition, recent evidence shows that downregulation of miR-145 levels in EOC samples induces an increase in several oncoproteins and thus, promotes EOC progression [ 39 , 40 , 41 , 42 , 43 ].…”

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

“…MiR-145, located in a fragile region of chromosome 5q has been reported to play a tumor suppressor role in a variety of other cancers, including NB [19]. As a cancer suppressor gene, it inhibits proliferation, invasion, and metastasis of tumor cells, increases sensitivity to chemotherapeutic drugs, and regulates the development and progression of tumors [20,21]. Decreased miR-145 expression has reported in a wide range of tumors including prostate, bladder, colon, ovarian, and esophageal cancers, suggesting a potential role in disease pathology.…”

“…Decreased miR-145 expression has reported in a wide range of tumors including prostate, bladder, colon, ovarian, and esophageal cancers, suggesting a potential role in disease pathology. In-depth studies suggest that miR-145 could be an ideal marker for diagnostic and prognostic evaluations of tumors, and that it may also represent a novel target for cancer treatment [21,22]. However, the role of miR-145 in NB is still unclear.…”

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

“…MiR-145 is a newly discovered miR with signi cantly downregulated expression in breast cancer, cervical cancer, glioma, colon cancer, esophageal cancer, and nonsmall cell lung cancer [25,26]. Many recent studies have found that microRNA is closely related to ovarian cancer [27,28].…”