miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway

Cheng, Zhenguo; Liu, Funan; Zhang, Hongyan; Li, Xiaodong; Li, Yanshu; Li, Jiabin; Liu, Furong; Cao, Yu; Cao, Liu; Feng, Li

doi:10.18632/oncotarget.16098

Cited by 39 publications

(38 citation statements)

References 47 publications

(45 reference statements)

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“…The results of the present study suggest that FAK phosphorylation was decreased following NTN1 knockdown in GC cells, whereas NTN1 overexpression had the opposite effect. GC cell proliferation was significantly inhibited following pretreatment with FAK inhibitor, which is consistent with previous results (26,27). These results indicate that dysfunction of FAK signaling pathway may be an important mechanism involved in GC cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

et al. 2018

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Netrin‑1 (NTN1) has been demonstrated to promote tumorigenesis in multiple types of cancer; however, its role in the growth of gastric cancer (GC) cells has not been described in detail. In the present study, the data suggested that NTN1 knockdown significantly decreased the proliferation of GC cells, whereas NTN1 overexpression had an opposing effect. Furthermore, the use of focal adhesion kinase (FAK) inhibitor decreased the proliferation of GC cells. It was also revealed that NTN1 markedly induced the phosphorylation of FAK, extracellular signal‑regulated kinase (ERK) and c‑Jun N‑terminal kinase (JNK), but did not induce the phosphorylation of P38. In addition, the expression of ERK and JNK was markedly inhibited by treatment with FAK inhibitor. Xenograft analysis using GC cells revealed that NTN1 overexpression promoted tumor growth. Furthermore, the expression of NTN1 in samples collected from nude mice was downregulated in the NTN1 knockdown group and upregulated in the NTN1 overexpression group compared with the control short hairpin RNA group. These results suggest that NTN1‑induced GC cell proliferation is mediated by activating ERK/MAPK signaling cascades via the distinct activation of FAK.

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Section: Discussionsupporting

confidence: 92%

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

et al. 2018

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“…MIR135A1 was herein identified as one of the most frequently deleted miRNA genes at the short arm of human chromosome 3 and predicted for poorer survival in patients with breast cancer, suggestive of a tumor suppressive role of miR-135a, which was confirmed by our in vitro and in vivo studies. Our observations are consistent with other previous studies showing that miR-135a suppresses tumor growth and metastasis of breast cancer (44)(45)(46). In contrast, miR-135a has been reported to promote breast cancer invasion and migration through mediating the depletion of metastasis suppressor, HOXA10 (33).…”

Section: Discussionsupporting

confidence: 93%

Loss of Estrogen-Regulated MIR135A1 at 3p21.1 Promotes Tamoxifen Resistance in Breast Cancer

Zhang

Chong

et al. 2018

Cancer Research

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The dysregulation of miRNAs has been increasingly recognized as a critical mediator of cancer development and progression. Here, we show that frequent deletion of the locus is associated with poor prognosis in primary breast cancer. Forced expression of miR-135a decreased breast cancer progression, while inhibition of miR-135a with a specific miRNA sponge elicited opposing effects, suggestive of a tumor suppressive role of miR-135a in breast cancer. Estrogen receptor alpha (ERα) bound the promoter of for its transcriptional activation, whereas tamoxifen treatment inhibited expression of miR-135a in ERα breast cancer cells. miR-135a directly targeted and, forming a negative feedback loop to inhibit ERα signaling. This regulatory feedback between miR-135a and ERα demonstrated that miR-135a regulated the response to tamoxifen. The tamoxifen-mediated decrease in miR-135a expression increased the expression of miR-135a targets to reduce tamoxifen sensitivity. Consistently, miR-135a expression was downregulated in ERα breast cancer cells with acquired tamoxifen resistance, while forced expression of miR-135a partially resensitized these cells to tamoxifen. Tamoxifen resistance mediated by the loss of miR-135a was shown to be partially dependent on the activation of the ERK1/2 and AKT pathways by miR-135a-targeted genes. Taken together, these results indicate that deletion of the locus and decreased miR-135a expression promote ERα breast cancer progression and tamoxifen resistance. Loss of miR-135a in breast cancer disrupts an estrogen receptor-induced negative feedback loop, perpetuating disease progression and resistance to therapy. http://cancerres.aacrjournals.org/content/canres/78/17/4915/F1.large.jpg .

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“…miR-135a was derived from miR-135a-2 locus embedded in RMST [49,50]. Functional enrichment analysis with StarBase software identified 17 pathways [51]. Of them, the TGF-beta signalling pathway and IGF1/PIK3/AKT signalling pathway might be correlated to the pathogenesis of ARC [16,47,52].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

Liu

Shan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Age-related cataract (ARC) remains the leading cause of visual impairment among the elderly population. Long non-coding RNAs (lncRNAs) have emerged as potential regulators in many ocular diseases. However, the role of lncRNAs in nuclear ARC, a subtype of ARC, requires further elucidation. Methods: LncRNA sequencing was performed to identify differentially expressed lncRNAs between the capsules of transparent and nuclear ARC lenses. Expression validation was confirmed by qRT-PCR. MTT assay, Calcein-AM and propidium iodide double staining, Rhodamine 123 and Hoechst double staining, EdU and transwell assay were used to determine the role of H19 or miR-675 in the viability, apoptosis, proliferation and migration of primary cultured human lens epithelial cells (HLECs). Bioinformatics and luciferase reporter assays were used to identify the binding target of miR-675. Results: Sixty-three lncRNAs are differentially expressed between the capsules of transparent and nuclear ARC lenses. One top abundantly expressed lncRNA, H19, is significantly up-regulated in the nuclear ARC lens capsules and positively associated with nuclear ARC grade. H19 knockdown accelerates apoptosis development and reduces the proliferation and migration of HLECs upon oxidative stress. H19 is the precursor of miR-675, and a reduction of H19 inhibits miR-675 expression. miR-675 regulates CRYAA expression by targeting the binding site within the 3’UTR. Moreover, miR-675 increases the proliferation and migration while decreasing the apoptosis of HLECs upon oxidative stress. Conclusion: H19 regulates HLECs function through miR-675-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of nuclear ARC.

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miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway

Cited by 39 publications

References 47 publications

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

Loss of Estrogen-Regulated MIR135A1 at 3p21.1 Promotes Tamoxifen Resistance in Breast Cancer

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

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