miR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4

Gao, Ling; Yang, Yijin; Xu, Haiyan; Liu, Ruqian; Li, Dechun; Han, Hong; Qin, Mingde; Wang, Yunliang

doi:10.1007/s13277-014-2092-9

Cited by 47 publications

(31 citation statements)

References 32 publications

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“…miR-335 serves as a tumor suppressor miRNA, is transcribed from the genomic region on chromosome 7q32.2 (76) and is downregulated in various human digestive malignancies, such as pancreatic carcinoma, hepatocellular carcinoma, colorectal cancer and gastric cancer (77)(78)(79)(80). A similar result was also observed in GBC patients.…”

Section: Tumor Suppressor Micrornassupporting

confidence: 56%

The role of microRNAs in gallbladder cancer

Yang

Zhang

et al. 2016

Molecular and Clinical Oncology

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Abstract. MicroRNAs (also referred to as miRNAs or miRs) play a crucial role in post-transcriptional gene regulation and serve as negative gene regulators by controlling a variety of target genes and regulating diverse biological processes, such as cell proliferation, invasion, migration and apoptosis. Aberrant expression of miRNAs is associated with the development and progression of cancer. Recent studies have reported that miRNAs may repress or promote the expression of cancer-related genes via several different signaling pathways in gallbladder cancer (GBC) patients and may function as tumor suppressors or oncogenes, thus providing a promising tool for the diagnosis and therapeutics of GBCs. In this review, we summarize the role of dysregulawted miRNA expression in the signaling pathways implicated in GBC and discuss the significant role of circulating miRNAs in GBC. Therefore, miRNAs may serve as novel therapeutic targets as well as diagnostic or prognostic markers in GBC.

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Section: Tumor Suppressor Micrornassupporting

confidence: 56%

The role of microRNAs in gallbladder cancer

Yang

Zhang

et al. 2016

Molecular and Clinical Oncology

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“…Wang et al (30) reported that miR-335 could directly suppress B-cell lymphoma 2 and lead to inhibition of the proliferation and invasion in renal cell carcinoma cells. Gao et al (18) reported that miR-335 could target the regulatory oncoprotein c-Met and suppress the migration of breast cancer cells. However, miR-335 also functions as a tumor oncogene in certain types of cancer.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma

Wang

Zeng

et al. 2017

Oncology Letters

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MicroRNA (miR)-335 and Rho-associated serine-threonine protein kinase 1 (Rock1) is ectopically expressed in multiple malignant tumors including osteosarcoma. The present study aimed to clarify whether the combined ectopically expressed miR-335 and Rock1 was correlated with clinicopathological features and prognosis in patients with osteosarcoma. The expression of miR-335 and Rock1 in 91 osteosarcoma tissue samples and 47 noncancerous bone tissues were determined respectively by in situ hybridization and immunohistochemistry. The association between miR-335 and Rock1 expression with the clinicopathological features of osteosarcoma was calculated using the Pearson's χ2 test. Spearman's correlation analysis was used to study the association between the miR-335 and Rock1 expression. Survival curves were drawn using the Kaplan-Meier method. Univariate and multivariate analysis was performed using the Cox's proportional hazard regression model to allow the prognostic values to be assessed. Expression levels of miR-335 were significantly reduced in osteosarcoma tissues (P<0.001), compared with that in noncancerous bone tissues, while Rock1 expression was significantly increased in osteosarcoma tissues (P<0.001). A strong correlation between miR-335 and Rock1 expression was also shown (P<0.001). Decreased miR-335 expression was identified to be positively associated with higher clinical stage (P=0.004) and distant metastasis (P=0.016), while elevated expression levels of Rock1 was positively associated with a larger tumor size (P=0.013), higher clinical stage (P=0.027) and distant metastasis (P=0.022). The combined high expression of Rock1 and low expression of miR-335 was clearly associated with distant metastasis (P=0.010) and a higher clinical stage (P=0.010). Patients with elevated Rock1 or decreased miR-335 expression exhibited a worse overall survival (OS) and disease-free survival (DFS) compared with patients with decreased Rock1 or increased miR-335 (P<0.001 for the two). In addition, patients with decreased miR-335 and increased Rock1 had the worst OS and DFS (P<0.001 for the two). In multivariate survival analysis, clinical stage (P=0.002 for DFS, P=0.015 for OS), distant metastasis (P=0.024 for DFS, P=0.002 for OS), low expression of miR-335 (P<0.001 for DFS, P=0.002 for OS) and combined depressed miR-335 and elevated Rock1 (P=0.021 for DFS, P=0.050 for OS) expression remained as the independent prognostic factors for DFS and OS. The present findings suggest that there may be an association between the combined downregulation of miR-335 and upregulation of Rock1 with tumor progression and adverse prognosis in patients with osteosarcoma.

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“…Though lacking a broader-scale underling mechanism study, miR-335 has been revealed as a PC inhibitor by Gao et al, targeting OCT4 [16]. Therefore, the mechanism was of great significance in pancreatic cancer studies.…”

Section: Discussionmentioning

confidence: 99%

circZMYM2 Competed Endogenously with miR-335-5p to Regulate JMJD2C in Pancreatic Cancer

Cai

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: We aimed to study the involvement of circZMYM2 (hsa_circ_0099999) in pancreatic cancer (PC) cell proliferation, apoptosis and invasion and to figured out the underlying mechanism of circZMYM2 regulating miR-335-5p and JMJD2C. Methods: CircRNA differential expressions in twenty PC samples and paired normal tissue samples were analyzed using Arraystar Human CircRNA microarray V1. CircZMYM2 expression level was determined via qRT-PCR. The effects of circZMYM2 inhibition and overexpression on cell proliferation, cell apoptosis and cell invasion were investigated by CCK-8 assays, Flow cytometry assays and Transwell assays. An animal experiment on nude mice was put forward to test the influence of circZMYM2 knockdown on tumor growth. The relationship between circZMYM2, miR-335 and JMJD2C was verified by RNA pull down, dual-luciferase reporter assays and rescue experiment. The effect of circZMYM2 and miR-335-5p on the expression of JMJD2C protein was detected by western blot. Results: CircZMYM2 overexpression was observed in both PC tissues and cells. Knockdown of circZMYM2 inhibited proliferation, induced apoptosis, and weakened invasion ability of cancer cells. Tumor growth was restrained in vivo. CircZMYM2 repressed the expression of its target miR-335-5p. MiR-335-5p attenuated pancreatic cancer development via inhibition of JMJD2C. Conclusion: Our study demonstrated that circZMYM2 promoted PC progression. CircZMYM2 had a sponge effect on miR-335-5p and modulated the downstream oncogene JMJD2C.

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miR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4

Cited by 47 publications

References 32 publications

The role of microRNAs in gallbladder cancer

The role of microRNAs in gallbladder cancer

MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma

circZMYM2 Competed Endogenously with miR-335-5p to Regulate JMJD2C in Pancreatic Cancer

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