MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance

Iqbal, Mohammad Askandar; Arora, Shweta; Prakasam, Gopinath; Calin, George A.; Syed, Mansoor Ali

doi:10.1016/j.mam.2018.07.003

Cited by 343 publications

(243 citation statements)

References 235 publications

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“…An accumulation of evidence has indicated that abnormal miRNA expression is an indication of different types of cancer, including EC (11,22,23). The dysregulation of miRNAs may serve an important role in the development and progression of EC by regulating a variety of processes, including cell proliferation, apoptosis, cycle, differentiation, metastasis and sensitivity of radiotherapy and chemotherapy (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑873 inhibits the proliferation and invasion of endometrial cancer cells by directly targeting hepatoma‑derived growth factor

Wang

Zhu

2019

Exp Ther Med

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An accumulation of evidence has demonstrated that abnormal microRNA (miRNA or miR) expression is associated with different types of cancer, including endometrial cancer (EC). The dysregulation of miRNAs may serve important roles in the development and progression of EC by regulating multiple aggressive biological behaviors, including cell proliferation, apoptosis, metastasis and angiogenesis. An in-depth understanding of the miRNAs associated with EC initiation and progression may be crucial for identifying successful therapeutic techniques. miR-873 has been demonstrated to be dysregulated in different types of cancer. However, the expression status and regulatory roles of miR-873 are yet to be elucidated in EC. In the present study, reverse transcription-quantitative PCR was carried out to detect miR-873 expression in EC tissues and cell lines. Cell Counting Kit-8 and in vitro invasion assays were utilized to determine the influence of miR-873 on the proliferation and invasion of EC cells. miR-873 expression was revealed to be downregulated in EC tissues and cell lines. Decreased miR-873 expression was significantly associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis of patients with EC. Functional assays revealed that resumed miR-873 expression suppressed the proliferation and invasion of EC cells. Additionally, hepatoma-derived growth factor (HDGF) was indicated to be a direct target gene of miR-873 in EC cells. HDGF was highly expressed in EC tissues and inversely correlated with miR-873 expression. HDGF silencing also imitated the tumor-suppressor activity of miR-873 overexpression in EC cells. A series of rescue experiments identified that recovered HDGF expression hindered the anti-proliferative and anti-invasive roles of miR-873 upregulation in EC cells. In conclusion, the present study indicated that miR-873 serves an important role as a tumor suppressor in EC development by directly targeting HDGF. The results may provide a novel insight into clinical treatments, which can be used to prevent EC aggression.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑873 inhibits the proliferation and invasion of endometrial cancer cells by directly targeting hepatoma‑derived growth factor

Wang

Zhu

2019

Exp Ther Med

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“…In this manner, miRNAs have been demonstrated to serve crucial roles in a wide range of physiological processes including cell proliferation, cell cycle progression, differentiation, metabolism, metastasis and tumorigenesis (14). In particular, accumulating evidence supports that miRNAs are aberrantly expressed in a substantial number of human disorders including cancer (15)(16)(17); with changes in miRNA expression being reported in HCC (18), colorectal cancer (19), lung cancer and bladder cancer (20,21). In HCC alone, miRNAs have been implicated either as oncogenes or tumor suppressors during oncogenesis and development (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein�1

et al. 2019

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Emerging studies have revealed that microRNAs (miRNAs) are aberrantly expressed in hepatocellular carcinoma (HCC), and the dysregulation of miRNAs exerts crucial roles in the carcinogenesis and development of HCC. Therefore, elucidating the relationship between miRNAs and HCC progression is of great importance to develop novel therapeutic techniques and to improve the prognosis of patients with this malignancy. Recently, miR-548b-3p (miR-548b) has been demonstrated to be a cancer-associated miRNA in tongue squamous cell carcinoma and glioma. However, the expression and function of miR-548b in HCC remain poorly understood. In the present study, it was found that miR-548b is expressed at low levels in HCC tissues and cell lines. Decreased miR-548b expression was found to be positively associated with the clinical features of HCC, including the TNM stage and lymph node metastasis. Functional experiments revealed that upregulation of miR-548b expression decreased proliferation and invasion of HCC cells. Specificity protein 1 (SP1) was verified to be a direct target of miR-548b in HCC cells; as Spearman's correlation analysis identified miR-548b expression to be negatively correlated with that of SP1 expression in HCC tissue specimens. In addition, SP1 inhibition exhibited similar effects as miR-548b overexpression in HCC cells. SP1 reintroduction significantly reversed the suppressive effects of miR-548b upregulation on the proliferation and invasion of HCC cells. In conclusion, the results presented in the present study demonstrated that miR-548b may serve as a tumor suppressive miRNA that inhibits the proliferation and invasion of HCC cells by directly targeting SP1. Consequently, miR-548b can be exploited as a novel therapeutic target for treating patients with HCC in the future, but this needs to be investigated further.

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“…The KEGG pathway analysis indicated that some of candidate genes were participated in microRNAs in cancer, CAMs, and signaling pathways regulating pluripotency of stem cells. Like other miRNAs, miR-204-5p plays an indispensable role in cancer proliferation, migration, and metastasis by regulating the tumor microenvironment, such as ECM structure and CAM metabolism [64]. Cancer stem cells (CSCs) attain stemness by complicated processes and signaling pathways, such as JAK-STAT, nuclear factor kappa B, Sonic hedgehog, transforming growth factor beta, Wnt/β-catenin, and PI3K/AKT [65,66].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses

Liang

Gan

et al. 2020

Respir Res

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Background: Pulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC). Methods: Expression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references. Results: The expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation. Conclusions: The frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p.

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MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance

Cited by 343 publications

References 235 publications

MicroRNA‑873 inhibits the proliferation and invasion of endometrial cancer cells by directly targeting hepatoma‑derived growth factor

MicroRNA‑873 inhibits the proliferation and invasion of endometrial cancer cells by directly targeting hepatoma‑derived growth factor

MicroRNA‑548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein�1

Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses

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