MiR-491-5p, as a Tumor Suppressor, Prevents Migration and Invasion of Breast Cancer by Targeting ZNF-703 to Regulate AKT/mTOR Pathway

Guo, Jingyun; Luo, Can; Yang, Yuqin; Dong, Jianyu; Guo, Zhaoze; Yang, Jinlamao; Lian, Huining; Ye, Changsheng; Liu, Minfeng

doi:10.2147/cmar.s279747

Cited by 23 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Aoki and Fujishita study [25] found that the AKT/ mTOR signaling pathway significantly impacts the development and prognosis of malignant tumors. In addition, aberrant activation of the AKT/mTOR pathway can lead to malignant tumor proliferation, blocked apoptosis, accelerated circulatory manipulation, angiogenesis, invasion, and metastasis [26][27][28][29]. To further investigate its mechanism of action, we used western blot to detect Akt, p-Akt, mTOR, and p-mTOR protein levels in overexpressed or silenced ZNF488 cells.…”

Section: Discussionmentioning

confidence: 99%

ZNF488 Promotes the Invasion and Migration of Pancreatic Carcinoma Cells through the Akt/mTOR Pathway

Qiu

Zhang

Wang

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Objective. Studies have demonstrated that zinc finger protein 488 (ZNF488) is highly expressed in pancreatic carcinoma (PC), but its effect on PC and its molecular mechanism remains unclear. Methods. Real-time fluorescent quantitative PCR (RT-qPCR) was employed to detect the ZNF488 expression in PC patients’ cancer tissues and cell lines. After interfering with or overexpressing ZNF488 in PANC-1 and AsPC-1 cells, respectively, the CCK-8, cell cloning, Transwell, and scratch assays were performed to detect cell proliferation, cell viability, invasion ability, and migration ability. In addition, Western blot was applied to assess the protein expression of Akt, p-Akt, mTOR, and p-mTOR in the Akt-mTOR pathway. Results. The ZNF488 expression was evidently raised in PC tissues and cell lines, and the starBase V3.0 database indicated that the higher the ZNF488 expression, the lower the survival rate of PC patients. Furthermore, we discovered that overexpressing ZNF488 can markedly promote the proliferation, invasion, and migration of PC cells. At the same time, highly expressed ZNF488 distinctly increased the p-Akt and p-mTOR expressions and the p-Akt/Akt and p-mTOR/mTOR ratios. However, after knocking down the ZNF488 expression, it had the opposite results. In addition, the Akt agonist SC79 can alleviate the effect of ZNF488 knockdown on Akt/mTOR pathway-related proteins, while Akt inhibitor AZD5363 had the opposite effect. Conclusion. ZNF488 could promote the proliferation, invasion, and migration of PC cells, and its mechanism may be related to the activation of the Akt/mTOR pathway. This study demonstrated that ZNF488 could be used as a molecular target for diagnosing and treating PC.

show abstract

Section: Discussionmentioning

confidence: 99%

ZNF488 Promotes the Invasion and Migration of Pancreatic Carcinoma Cells through the Akt/mTOR Pathway

Qiu

Zhang

Wang

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

show abstract

“…Various directly targeted proteins by miR-491-5p in many cancers have been recognized such as hTERT and JMJD2A in cervical cancer [13,14], BCL-XL and EGFR in ovarian cancer [15], Wnt3a and Notch3 in gastric cancer [16,63], TP53 and Bcl-XL in pancreatic cancer [17], G-protein-coupled receptor kinase-interacting protein 1 (GIT1) in OSCC [19] and FOXP4 in osteosarcoma [20]. Although miR-491-5p was also found to target JMJD2B and ZNF-703 to act as a tumor suppressor in breast cancer as mentioned previously [9,10,12], no investigations to pinpoint that RABIF is a direct target of miR-491-5p in breast cancer especially in TNBC in the past. RABIF was once to be identified as a new biomarker candidate of breast cancer development by a bioinformatics tool named PINCAGE (probabilistic integration of cancer genomics data for perturbed gene) [64].…”

Section: Discussionmentioning

confidence: 99%

Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer

Huang

Chi

Tung

et al. 2021

Cells

View full text Add to dashboard Cite

Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to development of chemoresistance and lack of effective endocrine or targeted therapies. MiR-491-5p has been found to play a tumor suppressor role in many cancers including breast cancer. However, the precise role of miR-491-5p in TNBC has never been elucidated. In this study, we reported the novel tumor suppressor function of FOCAD/miR-491-5p in TNBC. High expression of miR-491-5p was found to be associated with better overall survival in breast cancer patients. We found that miR-491-5p could be an intronic microRNA processed form FOCAD gene. We are the first to demonstrate that both miR-491-5p and FOCAD function as tumor suppressors to inhibit cancer stemness, epithelial-mesenchymal transition, drug resistance, cell migration/invasion, and pulmonary metastasis etc. in TNBC. MiR-491-5p was first reported to directly target Rab interacting factor (RABIF) to downregulate RABIF-mediated TNBC cancer stemness, drug resistance, cell invasion, and pulmonary metastasis via matrix metalloproteinase (MMP) signaling. High expression of RABIF was found to be correlated with poor clinical outcomes of breast cancer and TNBC patients. Our data indicated that miR-491-5p and RABIF are potential prognostic biomarkers and targeting the novel FOCAD/miR-491-5p/RABIF/MMP signaling pathway could serve as a promising strategy in TNBC treatment.

show abstract

“…In addition, miR-491-5p levels were found to be suppressed in cervical cancer cells by JMJD2A (Li et al, 2019). Recent database publications demonstrated the possible mechanisms of miR-491-5p in suppressing the migration and invasion of breast cancer by targeting ZNF-703 to regulate the AKT/mTOR pathway or via TPX2 targeting (Tan et al, 2019;Guo et al, 2021). Consistent with results obtained from previous studies, our findings showed that miR-491-5p can act as a tumor suppressor in breast cancer and that the regulation of miR-491-5p expression could affect breast cancer progression.…”

Section: Discussionmentioning

confidence: 99%

“…In ovarian cancer, miR-491-5p has been shown to induce apoptosis by overriding the antiapoptotic activities of BCL-X (L) and MCL1 (Denoyelle et al, 2014). Data from previous studies showed that miR-491-5p was associated with breast cancer progression (Tan et al, 2019;Guo et al, 2021). However, more evidence is required to gain a comprehensive understanding of the role of miR-491-5p in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the Oncogenic Role of VPS28 Modulated by miR-491-5p in Breast Cancer Cells Using In Silico and Functional Analysis

Shi

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Vacuolar protein sorting–associated protein 28 (VPS28), one of the four cytosolic proteins comprising the endosomal sorting complex required for the transport I (ESCRT-I) component, has been reported to be linked to various cancers. However, less evidence is available regarding the involvement of VPS28 in breast cancer. To this end, this study focused on exploring the function of VPS28 in breast cancer cells using the in silico analysis. VPS28 expression pattern data in breast cancer tissues were collected using the Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases and analyzed to assess the association of VPS28 with breast cancer prognosis. The elevated VPS28 expression was found in breast cancer tissues and was associated with a poor prognosis (p < 0.001). A higher VPS28 expression indicated a short survival duration (HR = 2.43; 95% CI: 1.44–4.1; p < 0.001). The CCLE database showed that VPS28 was expressed in breast cancer cell lines. The upstream targets of VPS28 were identified using the mirDIP, starBase, and TargetScan online tools. The correlation and binding relationship between miR-491-5p and VPS28 was analyzed. VPS28 or miR-491-5p gain and loss of function experiments were performed to verify their potential effect on the biological functions of breast cancer cells. Knockdown of VPS28 was shown to suppress the biological functions and enhance the apoptosis of breast cancer cell lines. Micro RNA-491-5p, identified as a posttranscriptional regulator of VPS28, was downregulated in breast cancer tissues. In contrast to the miR-491-5p inhibitor, the miR-491-5p mimic could suppress the migration, wound healing ability, and proliferation, while accelerating apoptosis. However, co-transfection of VPS28 and miR-491-5p counteracted the effect of the miR-491-5p mimic on breast cancer cell functions. Thus, our in silico analysis demonstrates that miR-491-5p can suppress breast cancer progression by attenuating the expression of VPS28.

show abstract

MiR-491-5p, as a Tumor Suppressor, Prevents Migration and Invasion of Breast Cancer by Targeting ZNF-703 to Regulate AKT/mTOR Pathway

Cited by 23 publications

References 32 publications

ZNF488 Promotes the Invasion and Migration of Pancreatic Carcinoma Cells through the Akt/mTOR Pathway

ZNF488 Promotes the Invasion and Migration of Pancreatic Carcinoma Cells through the Akt/mTOR Pathway

Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer

Deciphering the Oncogenic Role of VPS28 Modulated by miR-491-5p in Breast Cancer Cells Using In Silico and Functional Analysis

Contact Info

Product

Resources

About