Hsa-miR-326 targets <i>CCND1</i> and inhibits non-small cell lung cancer development

Sun, Chengcao; Huang, Chuanhe; Li, Shujun; Yang, Cuili; Xi, Yongyong; Wang, Liang; Zhang, Feng; Fu, Yunfeng

doi:10.18632/oncotarget.7071

Cited by 113 publications

(75 citation statements)

References 58 publications

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“…Wu et al (23) reported that miR-326 re-expression attenuated cell growth and motility and promoted cell apoptosis and cell cycle-arrest in colorectal cancer. Studies revealed that miR-326 decreased cell proliferation, viability, colony formation, migration and invasion, reversed chemoresistance and increased apoptosis and epithelial-to-mesenchymal transition of lung cancer (25,(44)(45)(46). These findings indicated that miR-326 could be developed as a therapeutic target for these human cancer types.…”

Section: Discussionmentioning

confidence: 93%

“…In addition, low miR-326 expression is an independent factor predicting poor prognosis for glioma patients (40). Downregulation of miR-326 is also observed in colorectal (23), pancreatic (24) and lung cancer (25). Previous studies have indicated that miR-326 may be investigated as a useful prognostic marker in human cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Several miR-326 targets, including Bcl-2 (38) in osteosarcoma, FSCN1 (39) and NOB1 (41) in gastric cancer, SMO (47) and PKM2 (43) in glioma and CCND1 (25), phox2a (44), SP1 (45) and ADAM17 (46) in lung cancer, have been identified. In the present study, KRAS was validated as a novel target of miR-326.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, miR-326 has been reported to be differentially expressed in various types of tissues and play important roles in tumourigenesis and tumour development (23)(24)(25). However, to the best of our knowledge, studies on the role of miR-326 in melanoma have not yet been conducted.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

Kang

Zhang

et al. 2017

Oncol Rep

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Abstract. Melanoma is the seventh most common malignancy in females and the fifth most common cancer in males worldwide. An increasing number of studies have reported that microRNA (miRNA) dysregulation is frequently observed in various types of human cancers, including melanoma. Abnormally expressed miRNAs play an important role in melanoma formation and progression by serving as potential biomarkers and therapeutic targets. Recently, miRNA-326 (miR-326) has been reported to be differentially expressed in various types of tissues and play important roles in tumourigenesis and tumour development. However, the expression levels, biological roles and underlying mechanisms of miR-326 in melanoma remain unknown. In the present study, we demonstrated that miR-326 was significantly downregulated in melanoma tissues and cell lines. Functional assays revealed that the enforced expression of miR-326 suppressed melanoma cell proliferation and invasion and increased cell apoptosis in vitro. Using bioinformatic analysis, Kirsten rat sarcoma viral oncogene homolog (KRAS) was predicted as a potential target of miR-326. Luciferase reporter assay confirmed that miR-326 could directly target the 3'-untranslated region of KRAS. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis revealed that miR-326 upregulation decreased the KRAS expression in melanoma cells at both the mRNA and protein level. Furthermore, KRAS was upregulated in melanoma tissues and inversely correlated with miR-326 expression. In addition, the KRAS knockdown phenocopied the tumour-suppressing effects of miR-326 overexpression on melanoma cells. The restoration of the expression of KRAS markedly reversed the antitumour effects induced by miR-326 overexpression in melanoma cells. Further experiments indicated that miR-326 inactivated the AKT and ERK signalling pathways in melanoma. Collectively, these results revealed that miR-326 serves as a tumour suppressor in melanoma by targeting KRAS and regulating the AKT and ERK signalling pathways, indicating that miR-326 may be a promising therapeutic target for melanoma patients.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

Kang

Zhang

et al. 2017

Oncol Rep

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“…BrdU incorporation ELISA assay [33] was performed, and results show that Palomid 529 dosedependently inhibited 786-O cell proliferation (Fig. 1C).…”

Section: Palomidmentioning

confidence: 92%

Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo

Zhou

Yin

Cheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Mammalian target of rapamycin (mTOR) is a valuable treatment target of renal cell carcinoma (RCC). Palomid 529 is a novel mTORC1/2 dual inhibitor. Methods: RCC cells were treated with different concentrations of Palomid 529. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by BrdU ELISA assay. Cell apoptosis was tested by the Hoechst-33342 nuclei staining assay and Histone DNA ELISA assay. mTOR signaling was tested by Western blotting assay and co-immunoprecipitation (IP) assay. The SCID mouse 786-O xenograft model was established to test RCC cell growth in vivo. Results: Palomid 529 exerted cytotoxic, anti-proliferative and pro-apoptotic activities in 786-O RCC cells. Palomid 529 disassembled mTORC1/2, causing de-phosphorylation of mTORC1/2 substrates. Bromodomain-containing protein 4 (BRD4) is a primary resistant factor of Palomid 529. Palomid 529-induced 786-O cell apoptosis was sensitized by BRD4 inhibitors or BRD4 silencing, but inhibited with BRD4 over-expression. Palomid 529-induced cytotoxicity in the primary human RCC cells was negatively correlated with BRD4 expression level. In vivo, Palomid 529 i.p. administration inhibited 786-O xenograft tumor growth in SCID mice. Its anti-tumor activity was further sensitized by co-administration of the BRD4 inhibitor JQ1. Cconclusion: Palomid 529 inhibits RCC cell growth in vitro and in vivo. BRD4 inhibition could further sensitize Palomid 529 against RCC cells.

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Downregulation of microRNA‐326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer

Huang,

Hsieh,

Shieh

et al. 2023

BioFactors

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Zinc finger protein ZNF322A is an oncogenic transcription factor. Overexpression of ZNF322A activates pro‐metastasis, cancer stemness, and neo‐angiogenesis‐related genes to enhance lung cancer progression. However, the upstream regulator of ZNF322A is not well defined. Dysregulation of microRNAs (miRNAs) can mediate cancer cell growth, migration, and invasion to promote tumorigenesis. Here, we uncover the mechanism of miRNA‐mediated transcriptional regulation in ZNF322A‐driven oncogenic events. ZNF322A harbors several putative miRNA‐binding sites in the 3′‐untranslated region (UTR). We validated that miR‐326 downregulated ZNF322A‐3′‐UTR luciferase activity and mRNA expression. Furthermore, miR‐326 suppressed the expression of ZNF322A‐driven cancer‐associated genes such as cyclin D1 and alpha‐adducin. Reconstitution experiments by ectopic overexpression of ZNF322A abolished miR‐326‐suppressed cancer cell proliferation and cell migration capacity. Moreover, miR‐326 attenuated ZNF322A‐induced tumor growth and lung tumor metastasis in vivo. Clinically, the expression of miR‐326 negatively correlated with ZNF322A mRNA expression in surgically resected tissues from 120 non‐small cell lung cancer (NSCLC) patients. Multivariate Cox regression analysis demonstrated that NSCLC patients with low miR‐326/high ZNF322A profile showed poor overall survival. Our results reveal that the deregulated expression of miR‐326 leads to hyperactivation of ZNF322A‐driven oncogenic signaling. Targeting the miR‐326/ZNF322A axis would provide new therapeutic strategies for lung cancer patients.

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Hsa-miR-326 targets CCND1 and inhibits non-small cell lung cancer development

Cited by 113 publications

References 58 publications

MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo

Downregulation of microRNA‐326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer

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