MiR-138-5p targeting LIMK1 suppresses breast cancer cell proliferation and motility

Li, Dengfeng; Song, Hongming; Wu, Tianqi; Xie, Dan; Hu, Jiashu; Zhao, Jie; Fang, Lin

doi:10.1039/c7ra09042k

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…The expression of LIMK was elevated in many kinds of tumours, especially highly invasive malignancies. LIMK 1 plays an important role in the invasion and metastases of tumours by regulating the actin cytoskeleton molecules . Recently, the significance of LIMK1 in tumorigenesis has aroused extensive concern .…”

Section: Discussionmentioning

confidence: 99%

“…Inactivated cofilin lost the ability of binding to actin filaments which improved the stability of F‐actin, resulting in the change of actin cytoskeleton . Several studies have now confirmed that the expression of LIMK1 is consistently elevated in the many kinds of tumours including breast cancer, ovarian cancer, colon cancer and gastric cancer . However, researchers have paid little attention to the role of LIMK1 in prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have reported that LIMK can promote the invasive and metastatic ability of tumours . What is more, it also participated in many kinds of biological behaviours including angiogenesis, proliferation, cell cycle and migration . Thus, LIMK1 has great potential to be a therapeutic target to prevent the invasion and metastasis of PCa.…”

Section: Introductionmentioning

confidence: 99%

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Up‐regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence

Huang

Lin

et al. 2020

J Cellular Molecular Medi

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This study aimed to explore the association between LIM domain kinase 1 (LIMK1) expression in prostate cancer (PCa) tissues with advanced pathological features, lymph node metastases and biochemical recurrence. A total of 279 PCa specimens from patients who underwent radical prostatectomy and 50 benign prostatic hyperplasia (BPH) specimens were collected to construct tissue microarray, which were subjected to immunohistochemical staining for LIMK1 expression subsequently. Logistic and Cox regression analysis were used to evaluate the relationship between LIMK1 expression and clinicopathological features of patients with PCa. Immunohistochemical staining assay demonstrated that LIMK1 expression was significantly higher in PCa than BPH specimens (77.1% vs 26.0%; P < .001). LIMK1 expression was significantly higher in positive lymph node specimens than corresponding PCa specimens (P = .002; P < .001).Up-regulation of LIMK1 was associated with prostate volume, prostate-specific antigen, prostate-specific antigen density, Gleason score, T stage, lymph node metastases, extracapsular extension and seminal vesicle invasion, and positive surgical margin.Multivariate logistic regression analysis demonstrated that LIMK1 was an independent risk factor for PCa lymph node metastasis (P < .05). Multivariate Cox regression analysis revealed that the up-regulation of LIMK1 was an independent risk factor for biochemical recurrence. Kaplan-Meier analysis indicated that up-regulation LIMK1 was associated with shortened biochemical-free survival (BFS) after radical prostatectomy (P < .001).In conclusion, LIMK1 was significantly up-regulated in PCa and positive lymph node specimens and correlated with lymph node metastasis and shortened BFS of PCa. The underlying molecular mechanism of LIMK1 in PCa should be further evaluated. K E Y W O R D S advanced pathological features, biochemical recurrence, LIM domain kinase 1, lymph node metastasis, prostate cancer

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Up‐regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence

Huang

Lin

et al. 2020

J Cellular Molecular Medi

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“…Horizontal movement ability by performing scratch wound healing assay and vertical movement ability by performing transwell migration and invasion assay was performed as described previously [ 35 ]. Gelatin zymography was performed as described previously [ 36 ] to analyze MMP-9 and MMP-2 activity using CM derived from miR-140-5p-KD or miR-140-5p-OE cells.…”

Section: Methodsmentioning

confidence: 99%

miR-140-5p Attenuates Hypoxia-Induced Breast Cancer Progression by Targeting Nrf2/HO-1 Axis in a Keap1-Independent Mechanism

Mahajan

Sitasawad

2021

Cells

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Hypoxia and oxidative stress significantly contribute to breast cancer (BC) progression. Although hypoxia-inducible factor 1α (Hif-1α) is considered a key effector of the cellular response to hypoxia, nuclear factor erythroid 2–related factor 2 (Nrf2), a master antioxidant transcription factor, is a crucial factor essential for Hif-1α-mediated hypoxic responses. Hence, targeting Nrf2 could provide new treatment strategies for cancer therapy. miRNAs are potential regulators of hypoxia-responsive genes. In a quest to identify novel hypoxia-regulated miRNAs involved in the regulation of Nrf2, we found that miR-140-5p significantly affects the expression of Nrf2 under hypoxia. In our study, miR-140-5p expression is downregulated in BC cells under hypoxic conditions. We have identified Nrf2 as a direct target of miR-140-5p, as confirmed by the luciferase assay. Knockdown of miR-140-5p under normoxic conditions significantly enhanced Nrf2/HO-1 signaling and tumor growth, angiogenesis, migration, and invasion in BC. In contrast, overexpression of miR-140-5p under hypoxic conditions revealed opposite results. Further silencing Nrf2 expression mimicked the miR-140-5p-induced anti-tumor effects. Consistent with the knockdown of miR-140-5p in vitro, mice injected with miR-140-5p-KD cells exhibited dramatically reduced miR-140-5p levels, increased Nrf2 levels, and increased tumor growth. In contrast, tumor growth is potently suppressed in mice injected with miR-140-5p-OE cells. Collectively, the above results demonstrate the importance of the Nrf2/HO-1 axis in cancer progression and, thus, targeting Nrf2 by miR-140-5p could be a better strategy for the treatment of Nrf2-driven breast cancer progression.

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“…10 Li et al showed that miR-138 posttranscriptionally regulated LIMK1 to suppress the proliferation of breast cancer cells. 11 These studies have revealed an important tumor suppress function of miR-138 in various cancers. Moreover, miR-138 has been demonstrated to function as a tumor suppressor in glioblastoma (GBM) via regulating EZH2/CDK4/6-E2F1 signal loop.…”

Section: Introductionmentioning

confidence: 99%

<p>Tumor Suppressor microRNA-138 Suppresses Low-Grade Glioma Development and Metastasis via Regulating IGF2BP2</p>

Yang

Liu

Cheng

et al. 2020

OTT

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Background: Low-grade gliomas (LGG), approximately constitute one-third of all types of gliomas, are prone to relapse and metastasis. is reported to be dysregulated in diverse human tumors and mainly function as a tumor suppressor. In this study, we analyzed the expression profile and function of miR-138 in LGG. Methods: Quantitative PCR (qPCR) and public database bioinformatics analysis were performed to determine the miR-138 levels in LGG. MiR-138 overexpression in LGG cells was achieved by miR-138 mimics transfection. Cell proliferation was assessed by CCK8, EdU and colony formation assays. Cell invasion and migration were analyzed by transwell and woundhealing assays. Xenograft model was employed to study the role of miR-138 in LGG growth in vivo. The target of miR-138 was validated by multiple methods, such as luciferase reporter assay, RT-qPCR and Western blot. Bioinformatics analysis was conducted to explore the molecular mechanisms by which miR-138 contributed to LGG progression. Results: miR-138 was significantly downregulated in LGG tumor tissues and low expression of miR-138 was significantly associated with poor prognosis as well as relapse and metastasis in LGG patients. Functional analysis indicated that ectopic miR-138 expression suppressed LGG cell growth and invasive phenotype in vitro, and inhibited tumor development in vivo. Moreover, miR-138 directly targeted and repressed insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) by targeting the 3ʹ-UTR of IGF2BP2, inhibiting epithelial to mesenchymal transition (EMT) to attenuate LGG aggressiveness. In addition, we found that elevated IGF2BP2 expression correlates with poor survival of LGG patients. Conclusion: miR-138 may function as a tumor inhibitor by directly inhibiting IGF2BP2 and suppressing EMT in the progression of LGG.

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MiR-138-5p targeting LIMK1 suppresses breast cancer cell proliferation and motility

Abstract: Breast cancer is the most frequently diagnosed female cancer.

Cited by 8 publications

References 40 publications

Up‐regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence

Up‐regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence

miR-140-5p Attenuates Hypoxia-Induced Breast Cancer Progression by Targeting Nrf2/HO-1 Axis in a Keap1-Independent Mechanism

<p>Tumor Suppressor microRNA-138 Suppresses Low-Grade Glioma Development and Metastasis via Regulating IGF2BP2</p>

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