Up-Regulation of miR-21 Expression Predicate Advanced Clinicopathological Features and Poor Prognosis in Patients with Non-Small Cell Lung Cancer

Tian, Lei; Shan, Weiyu; Zhang, Yufei; Lv, Xuejun; Li, Xuehua; Wei, Caiyun

doi:10.1007/s12253-015-9979-7

Cited by 31 publications

(24 citation statements)

References 30 publications

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“…The patients with high miR-21 expression had a higher tumor grade and were at higher risk of lymph node metastasis. 21 Over-expressing miR-21 in lung cancer cells could be released into circulation, leading to increased miR-21 levels in blood. 22 Shen et al investigated miRNA profiles in paired lung tumor tissues and plasma specimens from NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Zhao¹,

Liu²,

Xie³

et al. 2020

OTT

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Osteoclastogenesis is a key process in osteolytic bone metastasis (BM). Previous studies indicated that some miRNAs could regulate cancers progression and osteoclastogenesis. Our purpose was to investigate the roles of lung cancer cells-derived circulating miR-21 on osteoclastogenesis and its clinical significance in BM patients. Materials and Methods: The difference of miRNA expression in two lung cancer cell lines SBC-5 (with characteristic BM ability) and SBC-3 (without BM ability) were analyzed by microarray and qRT-PCR. Circulating miR-21 levels of lung cancer patients with or without BM were compared by qRT-PCR. The TRAP staining was used to investigate the effects of conditioned media from lung cancer cell lines or patients' plasma with different miR-21 levels on osteoclastogenesis. ROC curve was used to evaluate the diagnostic performance of circulating miR-21 in BM patients. Results: We found that miR-21 expression was specifically higher in SBC-5 than that in SBC-3 cells. The supernatants of SBC-5 cells with higher-level miR-21 promoted osteoclastogenesis. Moreover, we demonstrated that the circulating miR-21 level was significantly higher in BM patients than that in non-BM patients. The plasma from BM patients with higher-level miR-21 could also promote osteoclastogenesis. Mechanistically, lung cancer cells-derived circulating miR-21 could be transferred into osteoclast precursor cells and promote osteoclastogenesis probably by inhibiting PTEN. Finally, clinical data showed that circulating miR-21 had a potential for the diagnosis of BM. Conclusion: Overall, our findings suggested that circulating miR-21 played important roles in osteoclastogenesis of lung cancer patients and may serve as a biomarker to diagnose BM of lung cancer.

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Section: Discussionmentioning

confidence: 99%

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Zhao¹,

Liu²,

Xie³

et al. 2020

OTT

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“…It is also expressed in blood and hematopoietic cells, which, as mentioned, are sensitive to radiation, explaining the fall in circulating levels of this miRNA after 15 Gy whole thorax irradiation. MiR-21-5p is a well-known lung injury marker303132. But studies with changes in miR-21-5p after radiation have been limited to lung cancer cells2333 and not in irradiated lung tissue.…”

Section: Discussionmentioning

confidence: 99%

Changes in miRNA in the lung and whole blood after whole thorax irradiation in rats

Gao

Liu

Narayanan

et al. 2017

Sci Rep

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We used a rat model of whole thorax x-ray irradiation to profile the microRNA (miRNA) in lung and blood up to 4 weeks after radiation. MiRNA from normal and irradiated Wistar rat lungs and whole blood were analyzed by next-generation sequencing and the changes by radiation were identified by differential deRNA-seq 1, 2, 3 and 4 weeks after irradiation. The average total reads/library was 2,703,137 with a mean of 88% mapping to the rat genome. Detailed profiles of 100 of the most abundant miRNA in rat blood and lung are described. We identified upregulation of 4 miRNA, miR-144-5p, miR-144-3p, miR-142-5p and miR-19a-3p in rat blood 2 weeks after radiation that have not previously been shown to be altered after radiation to the lung. Ingenuity Pathway Analysis identified signaling of inflammatory response pathways. These findings will support development of early detection methods, as well as mechanism(s) of injury and mitigation in patients after radiotherapy or radiological accidents.

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“…Tian et al . showed that altered miR-21 expression is related to NSCLC occurrence, development, and survival analysis indicated that miR-21 expression is negatively correlated with NSCLC progression [33]. MiR-21 is also an important miRNA regulating radiosensitivity of human cancer cells [34, 35].…”

Section: Discussionmentioning

confidence: 99%

Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by targeting PDCD4 gene

Jiang

Zhu

2017

Oncotarget

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This study aims to explore the effects of microRNA-21 (miR-21) on radiosensitivity in non-small cell lung cancer (NSCLC) by targeting programmed cell deanth 4 (PDCD4) and regulating PI3K/AKT/mTOR signaling pathway. Cancer tissues and adjacent normal tissues were collected from 97 NSCLC patients who received a standard radiotherapy regimen. TUNEL assay was applied to determine cell apoptosis in tissues. The qRT-PCR assay was used to detect the expressions of miR-21 expression and PDCD4 mRNA. The protein expressions of PDCD4 and PI3K/AKT/mTOR signaling pathway-related proteins were determined by Western blotting. Colony formation assay was used to observe the sensitivity to radiotherapy of NSCLC cells. Flow cytometry was adopted to testify cell apoptosis. Compared with adjacent normal tissues, miR-21 expression was significantly increased and the mRNA and protein expressions of PDCD4 were decreased in NSCLC tissues. Higher miR-21 expression was associated with attenuated radiation efficacy and shorter median survival time. PDCD4 was the target gene of miR-21. The miR-21 mimics and siRNA-PDCD4 decreased the sensitivity to radiotherapy and cell apoptosis of A549 and H1299 cells and activated PI3K/AKT/mTOR pathway. The sensitivity of A549 and H1299 cells was strengthened in the miR-21 inhibitors group and the PI3K/AKT/mTOR inhibitors group. The siRNA-PDCD4 could reverse the effects of miR-21 inhibitors on sensitivity to radiotherapy and cell apoptosis of NSCLC cells. Our findings provide strong evidence that miR-21 could inhibit PDCD4 expression and activate PI3K/AKT/mTOR signaling pathway, thereby affecting the radiation sensitivity of NSCLC cells.

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Up-Regulation of miR-21 Expression Predicate Advanced Clinicopathological Features and Poor Prognosis in Patients with Non-Small Cell Lung Cancer

Cited by 31 publications

References 30 publications

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Changes in miRNA in the lung and whole blood after whole thorax irradiation in rats

Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by targeting PDCD4 gene

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