Dysfunction and ceRNA network of the tumor suppressor miR-637 in cancer development and prognosis

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs ranging from 17 to 25 nt in length. miR-637 is down-regulated in most cancers and up-regulated only in clear cell renal cell carcinoma (ccRCC). miR-637 can target 21 protein-coding genes, which are involved in the regulation of cell growth, cell cycle, cell proliferation, epithelial-mesenchymal transition (EMT), cancer cell invasion and metastasis, etc. In glioma, the transcription factor ZEB2 can bind to the miR-637 promoter region and inhibit miR-637 expression. Besides, miR-637 could be negatively regulated by competing endogenous RNA (ceRNAs) comprising 13 circular RNA (circRNAs) and 9 long non-coding RNA (lncRNAs). miR-637 is involved in regulating five signaling pathways, including the Jak/STAT3, Wnt/β-catenin, PI3K/AKT, and ERK signaling pathways. Low miR-637 expression was significantly associated with larger tumors and later tumor node metastasis (TNM) staging in cancer patients. Low miR-637 expression was also associated with poorer overall survival (OS) in cancer patients such as glioblastoma and low-grade gliomas (GBM/LGG), non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and ovarian cancer (OV). Low expression of miR-637 increases the resistance of colorectal cancer (CRC) and human cholangiocarcinoma (CHOL) cancer cells to three anticancer chemotherapeutics (gemcitabine (dFdC), cisplatin (DDP), and oxaliplatin (OXA)). Our work summarizes the abnormal expression of miR-637 in various cancers, expounds on the ceRNA regulatory network and signaling pathway involved in miR-637, and summarizes the effect of its abnormal expression on the biological behavior of tumor cells. At the same time, the relationship between the expression levels of miR-637 and its related molecules and the prognosis and pathological characteristics of patients was further summarized. Finally, our work points out the insufficiency of miR-637 in current studies and is expected to provide potential clues for future miR-637-related studies.

CircHIPK3 regulates fatty acid metabolism through miR-637/FASN axis to promote esophageal squamous cell carcinoma

“…Subsequently, predictions from ceRNA networks combined with bioinformatic methods and luciferase reporter assays indicated that miR-637 could bind to circHIPK3 and FASN. So far, miR-637 has been shown to be involved in a variety of malignant behaviors [58,72,73]. For example, in triple-negative breast cancer, ectopic expression of miR-637 significantly attenuated the promotion of proliferation, migration, and invasion induced by upregulation of circSEPT9 in TNBC cells [73].…”

Endocrine disruption of early uterine differentiation causes adenocarcinoma mediated by Wnt/β-catenin- and PI3K/AKT signaling

“…Recently, WNT3A-mediated activation of PI3K was demonstrated in colorectal cancer cells 69 . Additional connections between these pathways could be mediated by noncoding RNAs such as microRNAs or long noncoding RNAs 70 . Finally, stromal inflammation- and oxidative stress-induced genotoxicity and cell proliferation may promote cancer development through activation of NF-κB and PI3K/AKT signaling in epithelial cells 71,72 .…”

Circ_0000877 accelerates proliferation and immune escape of non‐small cell lung cancer cells by regulating microRNA‐637/E2F2 axis

“…In the field of scientific research on NSCLC cells, the earlier research confirmed that adenocarcinoma‐specific miR‐181‐5p, miR‐361‐5p, and miR‐30a‐3p were certified to be promising and effective candidates for early diagnosis NSCLC 15 . As a crucial miRNA, miR‐637 was abnormally expressed in multiple of cancer cells, which was able to target 21 genes to take part in modulating cell growth 16 . Report from Teng et al verified that miR‐637 suppression was linked to TNM stage and poor prognosis of NSCLC patients and served as a tumor suppressor in NSCLC 17 .…”

“…15 As a crucial miRNA, miR-637 was abnormally expressed in multiple of cancer cells, which was able to target 21 genes to take part in modulating cell growth. 16 Report from Teng et al verified that miR-637 suppression was linked to TNM stage and poor prognosis of NSCLC patients and served as a tumor suppressor in NSCLC. 17 E2F2 is a normative transcription factor, which joins in transcription regulation, cell cycle, and tumorigenesis.…”