MicroRNA-215 suppresses the proliferation, migration and invasion of non-small cell lung carcinoma cells through the downregulation of matrix metalloproteinase-16 expression

Non-small cell lung cancer (NSCLC) is one of the mostly deadly malignancies in the world. Nucleolin is a multifunctional protein that mainly regulates ribosome biogenesis but also has other functions including modulating the transcription of mRNAs and repressing RNA polymerase II. Nucleolin is overexpressed in various cancer cells, including NSCLC cells. It can confer resistance to apoptosis and promote cell migration and blood vessel formation by directly taking part in various tumor signal transduction pathways. The activities of nucleolin are regulated mainly by intracellular localization and post-translational modifications, including phosphorylation, glycosylation, methylation, and ADP-ribosylation. Phosphorylation of nucleolin (P-nucleolin) in NSCLC cells is still not well characterized. In the present study, the levels of nucleolin and P-nucleolin were examined in lung tissue and cells and it was demonstrated that levels of the two forms of nucleolin were significantly increased in NSCLC compared with non-cancerous tissues and cells. In addition, it was demonstrated that high expression levels of nucleolin and P-nucleolin were significantly associated with poor overall survival of NSCLC patients. Doxorubicin (DOX) is a type of anthracycline that has been used in the treatment of various types of cancer, including NSCLC. Upregulation of nucleolin through exogenous expression of nucleolin promoted A549 cell proliferation and migration, while downregulation of nucleolin through expression of small interfering RNA-nucleolin attenuated A549 cell proliferation and migration. Following stimulation with DOX, A549 cell proliferation and migration decreased and the expression of P-nucleolin also decreased. In order to investigate whether P-nucleolin is indispensable to the proliferation and migration of NSCLC cells, a plasmid encoding mutant nucleolin, in which the phosphorylation site at threonine-76 was mutated to alanine, was constructed. Compared with the A549 cells transfected with wild-type nucleolin, P-nucleolin expression and cell proliferation and migration were significantly decreased in A549 cells transfected with mutant nucleolin. These results indicate that targeting P-nucleolin may be a promising strategy for treating NSCLC patients.

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“…NSCLC cells, are considered key for oncogenicity (15), so DOX is also an important treatment for lung cancer.…”

Section: Phosphorylation Of Nucleolin Is Indispensable To Its Involvementioning

confidence: 99%

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Huang

Tan

et al. 2018

Oncol Rep

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“…Especially, increased microRNAs have been identified as lung cancer biomarkers (7). For example, miR-215 inhibited the progression of NSCLC through targeting MMP-16 (8). Wei and Ran (9) reported that miR-20a promoted proliferation and invasion by directly targeting EGR2 in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2

et al. 2019

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Increasing number of microRNAs (miRNAs) have been reported to play an important role in the development and progression of non-small cell lung cancer (NSCLC). In particular, microRNA-497-5p (miR-497-5p) has been proposed as a tumor suppressor miRNA in human cancers. However, the role of miR-497-5p and its potential molecular mechanism associated with NSCLC are less studied. Therefore, the role of miR-497-5p in the pathogenesis of NSCLC was investigated. In the present study, the expression of miR-497-5p was significantly downregulated in NSCLC. Moreover, overexpression of miR-497-5p inhibited the proliferation and invasion of NSCLC cells by suppressing FGF2. In addition, FGF2 was a downstream target of miR-497-5p in NSCLC. FGF2 was upregulated in NSCLC promoting cell proliferation and invasion. Overexpression of FGF2 impaired the inhibitory effect of miR-497-5p in NSCLC. Taken together, these results demonstrate that miR-497-5p is a tumor suppressor miRNA and demonstrate its potential for future use in the treatment of human NSCLC.

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“…However, miRNAs also participate in the occurrence and progress of various types of diseases, such as osteoporosis, myocardial infarction, diabetes mellitus, and Alzheimer's disease (8). Further, they are associated with cancer; some miRNAs are tumor suppressors, whereas others are oncogenic, such as miRNA-215 inhibits proliferation, migration, and invasion in NSCLC cells by inhibiting matrix metalloproteinase (MMP)-16, thereby serving as a potential therapeutic target for NSCLC in humans (9). miRNA-155-5p promotes autophagy in cervical cancer cells by targeting PDK1 and further inhibits the tumor progression in cervical cancers.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-374b inhibits the tumor growth and promotes apoptosis in non-small cell lung cancer tissue through the p38/ERK signaling pathway by targeting JAM-2

Wang¹,

Yu²,

Wang³

2018

J. Thorac. Dis

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Background: MicroRNAs (miRNAs) are reportedly involved in various cancers. The present study aimed to investigate the role of miRNA-374b in cell viability, proliferation, apoptosis, and tumor formation in nonsmall cell lung cancer (NSCLC) in humans. Methods: The expression level of miRNA-374b in blood and tumor tissues from NSCLC patients was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to assess the viability of NSCLC cells after transfection with miRNA-374b. Colony formation assay was performed to assess the proliferation of cells pretreated with miRNA-374b. The terminal deoxynucleotidyl transferase-dUTP nick-end labeling (TUNEL) assay was performed to determine the role of miRNA-374b in apoptosis in NSCLC cells. A tumor formation assay was performed to assess the effects of miRNA-374b on tumorigenesis in NSCLC. Results: miRNA-374b was markedly downregulated in the blood and tumor tissues from NSCLC patients. Furthermore, overexpression of miRNA-374b markedly reduced the viability of NSCLC cells, but miRNA-374b inhibitor increased the viability of NSCLC cells compared with that in negative controls. Moreover, miRNA-374b decreased the number of colonies; however, its corresponding anti-miRNA oligonucleotide (AMO) markedly increased colony formation by NSCLC cells. Also, miRNA-374b promoted the apoptosis and inhibited tumor formation in NSCLC; however, this inhibition was reversed upon treatment with the AMO. Western blot analysis revealed that miRNA-374b regulates tumor progression through the p38/ERK signaling pathway by inhibiting JAM-2 in NSCLC. Conclusions: The present results indicate that miRNA-374b inhibits tumor growth and promotes apoptosis in NSCLC through the p38/ERK signaling pathway by targeting JAM-2.

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MicroRNA-215 suppresses the proliferation, migration and invasion of non-small cell lung carcinoma cells through the downregulation of matrix metalloproteinase-16 expression

Cited by 15 publications

References 29 publications

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2

MicroRNA-374b inhibits the tumor growth and promotes apoptosis in non-small cell lung cancer tissue through the p38/ERK signaling pathway by targeting JAM-2

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