miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas

Lin, Shih-Shen; Peng, Cheng-Ming; Liao, Yi-Wen; Chou, Ming‐Yung; Hsieh, Pei‐Ling; Yu, Cheng–Chia

doi:10.3390/cancers10080272

Cited by 63 publications

(42 citation statements)

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“…The expression of miRNAs is associated with various human cancers, which indicates that there might be methods for us to make miRNAs as therapeutic targets for cancer therapy because miRNAs can modulate LncRNA and mRNA's gene expression [20]. Also, miRNAs' dysregulation can interrupt the inner balanced RNA networks, so, it may affect the progression of cancer [21].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1

Fan

Li²,

et al. 2020

Bioscience Reports

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Long non-coding RNA (lncRNA) FYVE, RhoGEF and PH domain containing 5 antisense RNA 1 (FGD5-AS1) has been reported as an oncogene in colorectal cancer, promoting its tumorgenesis. The present paper focused on searching the potential function of FGD5-AS1 in non-small cell lung carcinoma (NSCLC). There are connections between the expression of lncRNA FGD5-AS1 and human NSCLC tumor growth and progression. Also, the relationships between FGD5-AS1, hsa-miR-107 and mRNA fibroblast growth factor receptor like 1 (FGFRL1) are going to test their interaction in NSCLC cell lines, which may cause a series of biological behaviors of NSCLC cells. qRT-PCR analysis was conducted to test the expression of RNAs in different situation. CCK-8 experiment and clone formation assay were performed to assess proliferation of NSCLC cells. Also, connection between FGD5-AS1 and hsa-miR-107 were investigated by luciferase reporter assay and RNA pull-down assay. Rescue experiments were performed to verify the modulating relationship between FGD5-AS1, hsa-miR-107 and FGFRL1. High-level expression of FGD5-AS1 was found in NSCLC. FGD5-AS1 may promote the proliferation of NSCLC cells. Also, the combination between hsa-miR-107, FGD5-AS1 and NSCLC have been proved, which means they can play an interaction function in NSCLC cells. Thence, we concluded that lncRNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1

Fan

Li²,

et al. 2020

Bioscience Reports

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“…In addition, the correlation between miR‐1246 and the target gene CCNG2 still needs further study. Although the direct regulating relationship has been confirmed in oral, breast, pancreatic, and colorectal cancers we still need to clarify in LSCC.…”

Section: Discussionmentioning

confidence: 99%

Lack of miR‐1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2

et al. 2020

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Small extracellular vesicle (sEV) has precise impacts on tumor microenvironment and play vital functions in intercellular interaction. However, the functional role of sEV miRNA on laryngeal squamous cell carcinoma (LSCC) is largely unresolved. Here, the expression of miR‐1246 in LSCC tissues and plasma sEV was examined. The internalization ability of sEV was determined by uptake assay. Then, the source and purity of sEV were checked through RNase and/or pharmacological inhibitors application. The invasion, migration, proliferation, and cell cycle assays were used to determine the altered abilities of miR‐1246 in sEV in LSCC. Finally, target gene of miR‐1246, Cyclin G2 (CCNG2), was stained immunohistochemically. In addition, the relationship between CCNG2 and clinicopathological features of patients was analyzed. We found that miR‐1246 was higher in LSCC tissues and plasma sEV. MiR‐1246 was enriched in sEV rather than soluble form. SEV could be internalized into adjacent cells. Lack of miR‐1246 in sEV abrogated the tumorigenesis of LSCC. Furthermore, CCNG2 knockdown arrested the cell cycle and correlated to clinicopathological features and prognosis of LSCC patients. Taken together, we found that the function of sEV miR‐1246 by regulating CCNG2 is responsible for LSCC advancement with emphasis on the main source of miR‐1246 mainly root in sEV rather than in soluble form.

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“…Both miR-93-3p and miR-105-5p directly target SFRP1, thereby inducing the enhanced stemness of TNBC cells and resistance to cancer therapies via activating Wnt/β-catenin signaling [116]. Also, the cancer stemness of oral squamous cell carcinoma cells is enhanced by miR-1246, which targets cyclin G2 (CCNG2) [117]. CCNG2 serves as a negative regulator of Wnt/β-catenin signaling by modulating the expression of dishevelled segment polarity protein 2 (DVL2), LRP6, and β-catenin [118].…”

Section: Wnt/β-catenin Signaling-regulating Mirnasmentioning

confidence: 99%

“…CCNG2 serves as a negative regulator of Wnt/β-catenin signaling by modulating the expression of dishevelled segment polarity protein 2 (DVL2), LRP6, and β-catenin [118]. Indeed, knockdown of miR-1246 leads to a reduction in SOX2 expression [117]. In addition, a tumor suppressive miR-124-3p was identified to inhibit the self-renewal of non-small-cell lung cancer cells as a consequence of targeting ubiquitin specific peptidase 14 (USP14), which is a positive regulator of β-catenin expression [119,120] (Table 4).…”

Section: Wnt/β-catenin Signaling-regulating Mirnasmentioning

confidence: 99%

“…Over-expression of miR-145-5p sensitizes cells to cisplatin and 5-fluorouracil in gastric cancer. This miRNA also enhances the efficacy of radiation and oxaliplatin [144,145] miR-186-5p YY1 Glioblastoma Ectopic expression of miR-186-5p improves the cisplatin cytotoxicity [149] miR-195-5p NOTCH2, RBPJ Colorectal cancer Over-expression of miR-195-5p subdues resistance to 5-fluorouracil [126] miR-196-5p SOCS1, SOCS3 Colorectal cancer Knockdown of miR-196-5p sensitizes cancer cells to 5-fluorouracil by augmenting apoptosis [129] miR-324-5p SMO, GLI1 Multiple myeloma Over-expression of miR-324-5p heightens the efficacy of bortezomib in multiple myeloma cells [135] miR-381-3p NEFL Glioblastoma Silencing of miR-381-3p increases the sensitivity of cells to temozolomide [150] miR-423-5p ING4 Glioblastoma Over-expression of miR-423-5p significantly attenuates the chemosensitivity of glioma cells to temozolomide [137] miR-450b-5p SOX2 Colorectal cancer Ectopic expression of miR-450b-5p sensitizes cells to 5-fluorouracil [143] miR-589-5p SOCS2, SOCS5, PTPN1, PTPN11 Hepatocellular carcinoma Ectopic expression of miR-589-5p promotes the emergence of acquired resistance to doxorubicin [131] miR-873-5p PD-L1 Breast cancer Over-expression of miR-873-5p attenuates therapeutic resistance to doxorubicin [142] miR-1246 CCNG2 Oral cancer Knockdown of miR-1246 sensitizes cancer cells to cisplatin [117]…”

Section: Direct Regulation Of Stemness Factorsmentioning

confidence: 99%

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MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas

Cited by 63 publications

References 50 publications

Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1

Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1

Lack of miR‐1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

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