Downregulation of microRNA-33a promotes cyclin-dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation

Wang, Yudong; Zhou, Xin; Shan, Baoen; Han, Jing; Wang, Feifei; Fan, Xinyan; Lv, Yalei; Chang, Liang; Liu, Wei

doi:10.3892/mmr.2015.4296

Cited by 29 publications

(25 citation statements)

References 42 publications

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“…Kaplan-Meier analysis indicated that an overexpression of CCND1 affected the survival of GC patients. Existing studies have shown that forcing the expression of miR-33a can inhibit the overexpression of CCND1 and inhibit the proliferation of GC cells [41,42]. A study showed that CCND1 in MCF-7 breast cancer cells using CKI was significantly down-regulated compared with untreated cells [43].Therefore, CCND1 is predicted to be a significant target of CKI for the treatment of GC.…”

Section: Discussionmentioning

confidence: 99%

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

Zhou

Zhu

et al. 2020

BMC Complement Med Ther

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Background: As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out. Methods: In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Results: The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo. Conclusion: This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

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Section: Discussionmentioning

confidence: 99%

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

Zhou

Zhu

et al. 2020

BMC Complement Med Ther

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“…It is suggested that miR-33 may function as a tumor-associated molecule, as miR-33b can inhibit cell growth and induce apoptosis through suppressing the activity of WNT/β-catenin signaling in lung adenocarcinoma cells (40), and also inhibit the proliferation and migration of osteosarcoma cells by targeting hypoxia-inducible factor-1α (41). With further in-depth study of miR-33a, it was identified that mir-33a can also affect cell proliferation and cell cycle progression in tumors by regulating cyclin-dependent kinase 5, cyclin D1 and Pim-1 (42,43), inhibit bone metastasis by targeting parathyroid hormone-related protein (19), and inhibit cancer cell growth, invasion and metastasis by regulating the expression of high mobility group AT-hook 2 (44) and β-catenin (45). However, to the best of our knowledge, no report previously existed regarding the role of miR-33a in HCC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

Xie

Cong

Zhong³

et al. 2018

Oncol Lett

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Abstract. In order to examine the prognostic significance of miR-33a in patients with hepatocellular carcinoma (HCC), total RNA was extracted from 149 HCC biopsies, 36 of which were paired with para-carcinoma tissues, and miR-33a expression was measured by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that miR-33a expression was decreased in HCC biopsies compared with normal liver tissue samples. It was also demonstrated that miR-33a expression was significantly associated with tumor foci number. Furthermore, overall and progression-free survival time was decreased in patients expressing low miR-33a with multiple tumor foci. Taken together, the low expression of miR-33a may be a potential risk factor for HCC. IntroductionHepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide, and is associated with an extremely poor prognosis (1-3). A principal reason for the high mortality of this disease is the failure of early diagnosis for patients with HCC and the lack of effective therapies for patients with HCC in advanced stages. Despite a number of advances made in therapeutic strategies and surgery, the overall prognosis for patients with HCC remains poor due to the high rate of metastasis and recurrence (4-6). Hence, the characterization of the molecular mechanisms in HCC is urgently required to allow the development of novel treatment methods for patients with HCC.MicroRNAs (miRNAs/miRs) are small non-coding RNAs (21-23 nucleotides) that are transcribed as precursors in the nucleus and are subsequently processed into mature miRNAs in the cytoplasm. Mature miRNAs primarily function by sequence specific interactions with the 3'-untranslated regions of mRNAs, leading to the translational suppression or degradation of the mRNAs (7). An increasing number of studies have suggested that miRNAs serve an essential role as prognostic and predictive biomarkers in various types of cancer. For example, miR-1290 and miR-196b have been demonstrated to predict the chemotherapeutic response of patients with lung adenocarcinoma (8). miR-149, an anti-tumor miRNA, has been identified as dysregulated in a variety of types of cancer, including gastric (9), breast (10) and colorectal cancer (11,12).It is also reported that a number of are associated with HCC carcinogenesis, progression and metastasis, including miR-15b (13), miR-122 (14) and miR-29 (15). Furthermore, the low expression of miR-124 is significantly associated with a more aggressive phenotype and a poorer prognosis (16), whereas a high expression of miR-182 has been associated with intrahepatic metastasis and poor prognosis in HCC (17). However, the mechanism of these miRNAs and their regulatory networks in HCC remain elusive, and a number of miRNAs that are associated with HCC have yet to be considered.miR-33a was originally demonstrated to regulate lipid and cholesterol metabolism (18), and is an intronic miRNA located within the sequence of the sterol regulatory element binding protein 2 (SREBP-2) gene. miR-33a ...

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“…PIM1 expression has been reported to be modulated at transcriptional level through activation of JAK/STAT pathway in physiological conditions [ 34 ], however, its differential expression in tumor vs. normal cells might be induced through deregulation of microRNAs. Recently, several microRNAs including miR-33a have been found to directly target PIM1 in different cancer types [ 35 , 36 ]. Our data show strong deregulation of PIM1 expression level upon overexpression or knockdown of miR-33a in PCa cells, which indicates involvement of miR-33a in PCa pathogenesis through altering the oncogenic PIM1 level.…”

Section: Discussionmentioning

confidence: 99%

miR-33a is a tumor suppressor microRNA that is decreased in prostate cancer

et al. 2017

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Prostate cancer is one of the most frequently diagnosed neoplasms among men worldwide. MicroRNAs (miRNAs) are involved in numerous important cellular processes including proliferation, differentiation and apoptosis. They have been found to be aberrantly expressed in many types of human cancers. They can act as either tumor suppressors or oncogenes, and changes in their levels are associated with tumor initiation, progression and metastasis. miR-33a is an intronic miRNA embedded within SREBF2 that has been reported to have tumor suppressive properties in some cancers but has not been examined in prostate cancer. SREBF2 increases cholesterol and lipid levels both directly and via miR-33a action. The levels of SREBF2 and miR-33a are correlated in normal tissues by co-transcription from the same gene locus. Paradoxically, SREBF2 has been reported to be increased in prostate cancer, which would be predicted to increase miR-33a levels potentially leading to tumor suppression. We show here that miR-33a has tumor suppressive activities and is decreased in prostate cancer. The decreased miR-33a increases mRNA for the PIM1 oncogene and multiple genes in the lipid β-oxidation pathway. Levels of miR-33a are not correlated with SREBF2 levels, implying posttranscriptional regulation of its expression in prostate cancer.

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Downregulation of microRNA-33a promotes cyclin-dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation

Cited by 29 publications

References 42 publications

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

miR-33a is a tumor suppressor microRNA that is decreased in prostate cancer

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