Serum microRNA-135a downregulation as a prognostic marker of non-small cell lung cancer

Zhang, Y K; Sun, Bin; Sui, Guodong

doi:10.4238/gmr.15038252

Cited by 9 publications

(14 citation statements)

References 24 publications

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“…AUC of both predicted the prognosis of patients exceeded 0.80, indicating that both had higher prognostic value and might be independent prognostic indicators for NSCLC patients. In the studies by Zhang et al [28], the level of serum miR-135a is significantly lower in NSCLC patients, which is consistent with our research results. It has also pointed out that high level of miR-135a is significantly related to patients' distant metastasis, high TNM staging, low level of 5-year OS and other adverse prognosis.…”

Section: Discussionsupporting

confidence: 93%

miR-135a inhibits malignant proliferation and diffusion of non-small cell lung cancer cells by down-regulating ROCK1 protein

2020

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Objective: To seek the clinical significance and regulatory mechanism of miR-135a and Rho-associated protein kinase 1 (ROCK1) in non-small cell lung cancer (NSCLC). Methods: NSCLC cells were purchased, and miR-135a-mimics, miR-135a-inhibitor, miR-NC, si-ROCK1 and Sh-ROCK1 were transfected into NSCLC cells HCC827 and NCI-H524. qRT-PCR and Western blot were used to detect the expression of miR-135a, ROCK1, Bax, Caspase3, Bcl-2, N-cadherin, vimentin and E-cadherin. MTT, scratch test, Transwell and flow cytometry were used to analyze the cell proliferation, migration, invasion and apoptosis. Results: miR-135a was low expressed in serum of NSCLC group, while ROCK1 was opposite. miR-135a low level or ROCK1 high level was associated with poor prognosis of NSCLC and lower 3-year OS. Over-expression of miR-135a and inhibition of ROCK1 expression could control malignant growth and diffusion of cells and expression of Bcl-2, N-cadherin and vimentin proteins, and promote apoptosis and expression of Bax, Caspase3 and E-cadherin proteins. After transfection of miR-135a-mimics+sh-ROCK1 to HCC827 and NCI-H524, the malignant proliferation and diffusion behavior of the cells were not different from those of the miR-NC group with no transfection sequence. The double luciferase report revealed that miR-135a has a targeting relationship with ROCK1. Conclusion: miR-135a is abnormally down-regulated in NSCLC. As a serum indicator, miR-135a has the potential to diagnose NSCLC and predict prognosis. The up-regulated expression of miR-135a protein can down-regulate the ROCK1 protein, inhibit the malignant proliferation, migration, invasion, EMT and other diffusion behaviors of NSCLC cells, and increase the apoptosis ability of cells.

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Section: Discussionsupporting

confidence: 93%

miR-135a inhibits malignant proliferation and diffusion of non-small cell lung cancer cells by down-regulating ROCK1 protein

2020

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“…14 More than 50% of the miRNA genes have been located in tumor-related genomic regions or fragile sites. 28 Zhou's findings indicated that miR-135a promotes cell apoptosis and inhibits cell proliferation, migration, invasion, and tumor angiogenesis by targeting IGF-1 gene through the IGF-1/PI3K/Akt signaling pathway in NSCLC, 29 and MiR-135a inhibits migration and invasion and regulates EMT-related marker genes by targeting KLF8 in lung cancer cells, 30 which is consistent with our study, while Zhang's study showed that MiR-135a overexpression promoted viability, migration, and invasion, but inhibited apoptosis of NCI-H1650 and NCI-H1975 cells. The serum miR-135a level was downregulated in non-small-cell lung carcinoma (NSCLC) patients and was associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…It can be used as a biomarker for NSCLC prognosis. 28 Zhou's findings indicated that miR-135a promotes cell apoptosis and inhibits cell proliferation, migration, invasion, and tumor angiogenesis by targeting IGF-1 gene through the IGF-1/PI3K/Akt signaling pathway in NSCLC, 29 and MiR-135a inhibits migration and invasion and regulates EMT-related marker genes by targeting KLF8 in lung cancer cells, 30 which is consistent with our study, while Zhang's study showed that MiR-135a overexpression promoted viability, migration, and invasion, but inhibited apoptosis of NCI-H1650 and NCI-H1975 cells. 31 Our subsequent cell biology experiments supported our results that the overexpression of mir-135a-5p could inhibit the invasion of adenocarcinoma cells, and the overexpression of mir-542-3p could promote the proliferation of adenocarcinoma cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Analysis of differential expression profile of miRNA in peripheral blood of patients with lung cancer

Fang

et al. 2019

Clinical Laboratory Analysis

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Purpose To identify potential molecular targets for lung cancer intervention and diagnosis, we analyzed the differential miRNA expression of peripheral blood between lung cancer patients and healthy controls. Methods Three pairs of cases’ and controls’ peripheral blood samples were evaluated for miRNA expression by microarray. 12 miRNAs were selected for RT‐PCR validation and target genes prediction. In addition, 4 miRNAs were selected for future validation by RT‐PCR in a large sample of 145 cases and 55 frequency‐matched healthy controls. Results A total of 338 differentially expressed miRNAs were screened and identified by microarray. According to the fold changes, the top ten upregulated miRNAs were hsa‐miR‐124‐3p, hsa‐miR‐379‐5p, hsa‐miR‐3655, hsa‐miR‐450b‐5p, hsa‐miR‐29a‐5p, hsa‐miR‐200a‐3p, hsa‐miR‐542‐3p, hsa‐miR‐138‐5p, hsa‐miR‐219a‐2‐3p, and hsa‐miR‐4701‐3p, and the top ten downregulated miRNAs were hsa‐miR‐34c‐5p, hsa‐miR‐135a‐5p, hsa‐miR‐132‐3p, hsa‐miR‐3178, hsa‐miR‐4449, hsa‐miR‐4999‐3p, hsa‐miR‐1246, hsa‐miR‐4424, hsa‐miR‐1252‐5p, and hsa‐miR‐24‐2‐5p. RT‐PCR verification of the 12 miRNAs revealed that 5 of 8 upregulated miRNAs, 2 of 4 downregulated miRNAs showed a significant difference between the cases and controls (P < .05). A large number of target genes and their functional set showed overlapping among the 453 predicted target genes of the 12 miRNAs (P < .01). RT‐PCR in the large sample confirmed the significant differential expression level of hsa‐miR‐29a‐5p, hsa‐miR‐135a‐5p, hsa‐miR‐542‐3p, and hsa‐miR‐4491 between cases and controls (P < .05), and three of these microRNA, except hsa‐miR‐29a‐5p, were significant after Bonferroni correction for adjustment of multiple comparisons. Conclusion There was a significant difference in miRNAs expression in the peripheral blood between lung cancer patients and healthy controls, and 4 miRNAs were validated by a large‐size sample.

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“…An in vitro study also reported that miR-135a inhibited the migration and invasion of gastric cancer cells by targeting JAK2 [14]. With regards to the role of miR-135a in NSCLC, Zhang et al found that the expression of miR-135a was reduced in the sera of NSCLC patients and was related to poor prognosis [15]. Additionally, it has been reported that the overexpression or restoration of miR-135a represses proliferation and facilitates apoptosis of tumor cells by its target genes c-Myc in renal cell carcinoma [16], JAK2 in lymphoma [17], and ROCK1 in gastric cancer [18].…”

Section: Introductionmentioning

confidence: 99%

Effect of microRNA-135a on Cell Proliferation, Migration, Invasion, Apoptosis and Tumor Angiogenesis Through the IGF-1/PI3K/Akt Signaling Pathway in Non-Small Cell Lung Cancer

Zhou

et al. 2017

Cell Physiol Biochem

112

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Objective: This study explored the ability of microRNA-135a (miR-135a) to influence cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer (NSCLC). Methods: NSCLC tissues and adjacent normal tissues were collected from 138 NSCLC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-135a and IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 mRNA; western blotting was used to determine the expression levels of IGF-1, PI3K and Akt protein; and enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression levels of VEGF, bFGF and IL-8 protein. Human NSCLC cell lines (A549, H460, and H1299) and the human bronchial epithelial cell line (HBE) were selected. A549 cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, IGF-1 siRNA and miR-135a inhibitors + IGF-1 siRNA groups. The following were performed: an MTT assay to assess cell proliferation, a scratch test to detect cell migration, a Transwell assay to measure cell invasion, and a flow cytometry to analyze cell apoptosis. Results: The expression level of miR-135a was lower while those of IGF-1, PI3K and Akt mRNA were higher in NSCLC tissues than in the adjacent normal tissues. Dual-luciferase reporter assay indicated IGF-1 as a target of miR-135a. The in vitro results showed that compared with the blank group, cell proliferation, migration and invasion were suppressed, mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 were reduced, and cell apoptosis was enhanced in the miR-135a mimics and IGF-1 siRNA groups. Compared with the IGF-1 siRNA group, cells in the miR-135a inhibitors + IGF-1 siRNA group demonstrated increased cell proliferation, migration and invasion, elevated mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 and reduced cell apoptosis. Conclusion: These findings indicated that miR-135a promotes cell apoptosis and inhibits cell proliferation, migration, invasion and tumor angiogenesis by targeting IGF-1 gene through the IGF-1/PI3K/Akt signaling pathway in NSCLC.

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Serum microRNA-135a downregulation as a prognostic marker of non-small cell lung cancer

Cited by 9 publications

References 24 publications

miR-135a inhibits malignant proliferation and diffusion of non-small cell lung cancer cells by down-regulating ROCK1 protein

miR-135a inhibits malignant proliferation and diffusion of non-small cell lung cancer cells by down-regulating ROCK1 protein

Analysis of differential expression profile of miRNA in peripheral blood of patients with lung cancer

Effect of microRNA-135a on Cell Proliferation, Migration, Invasion, Apoptosis and Tumor Angiogenesis Through the IGF-1/PI3K/Akt Signaling Pathway in Non-Small Cell Lung Cancer

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