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Dysfunction and ceRNA network of the tumor suppressor miR-637 in cancer development and prognosis
Jinze Shen1, Chenhao Liang1, Xinming Su1
1Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China.
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.
Insights
MicroRNA 637 (miR-637) is often downregulated in cancers, impacting cell growth and metastasis. Its low expression correlates with poor prognosis and chemoresistance, highlighting its potential as a cancer biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression.
- miR-637 exhibits differential expression across cancers, notably downregulated in most but upregulated in clear cell renal cell carcinoma (ccRCC).
- Dysregulation of miR-637 is implicated in critical cancer processes including cell growth, proliferation, epithelial-mesenchymal transition (EMT), invasion, and metastasis.
Purpose of the Study:
- To summarize the aberrant expression patterns of miR-637 in various cancers.
- To elucidate the competing endogenous RNA (ceRNA) regulatory network and signaling pathways associated with miR-637.
- To analyze the impact of miR-637 dysregulation on tumor biological behavior, patient prognosis, and pathological characteristics.
Main Methods:
- Literature review and data synthesis on miR-637 expression and function in cancer.
- Analysis of regulatory mechanisms including transcription factor binding (ZEB2) and ceRNA interactions (circRNAs, lncRNAs).
- Investigation of miR-637's role in key signaling pathways (Jak/STAT3, Wnt/β-catenin, PI3K/AKT, ERK).
Main Results:
- Low miR-637 expression is linked to advanced tumor stage, larger tumor size, and poorer overall survival (OS) in glioblastoma, non-small cell lung cancer, hepatocellular carcinoma, and ovarian cancer.
- Reduced miR-637 levels enhance chemoresistance in colorectal and cholangiocarcinoma cells against gemcitabine, cisplatin, and oxaliplatin.
- miR-637 targets genes involved in cell cycle, EMT, invasion, and metastasis, and is regulated by ZEB2 and various non-coding RNAs.
Conclusions:
- Aberrant miR-637 expression significantly influences cancer progression, patient prognosis, and therapeutic response.
- The complex regulatory network involving ceRNAs and signaling pathways underscores miR-637's multifaceted role in oncology.
- Further research into miR-637 is warranted to explore its full potential as a diagnostic and therapeutic target in various cancers.
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