Dysregulation of MicroRNA-196b-5p and MicroRNA-375 in Gastric Cancer

Lee, Seung Woo; Park, Ki Cheol; Kim, Jeong Goo; Moon, Sung Jin; Kang, Sang Bum; Lee, Dong Hoon; Sul, Hae Joung; Ji, Jeong‐Seon; Jeong, Hyun Yong

doi:10.5230/jgc.2016.16.4.221

Cited by 30 publications

(26 citation statements)

References 51 publications

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“…miRNA-320b is down-regulated in various cancers, and it is associated with tumorigenesis and poor prognosis in glioma. 42 miRNA-375 was also shown to be often down-regulated in NSCLC, 43,44 breast cancer, 45 colorectal cancer, [46][47][48][49] oesophageal cancer, 50,51 gastric cancer, 52,53 and pancreatic cancer. 54,55 It is associated with tumour proliferation and metastases.…”

Section: Discussionmentioning

confidence: 99%

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

et al. 2018

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Immune checkpoint inhibitors, as nivolumab, are used in advanced non-small cell lung cancer (NSCLC). However, no associated biomarker is validated in clinical practice with this drug. We investigated herein immune-related blood markers in patients with advanced NSCLC treated with nivolumab. Plasma of 43 consecutive patients were prospectively collected at time of the diagnosis of cancer, at the initiation of nivolumab and at the first tumour evaluation (2 months). Concentrations of PD-L1 (sPD-L1), soluble PD-L2 (sPD-L2), Interleukine-2 (sIl-2), Interferon-gamma (sIFN-γ), and Granzyme B (sGranB) were quantified by ELISA. Cell free RNA was quantified by Reverse Transcriptase -PCR), and plasmatic microRNAs (miRNAs) were evaluated by targeted sequencing. Expression of PD-L1 on tumour biopsies was performed by immunohistochemistry using E13LN. High sPD-L1 at 2 months and increase of sPD-L1 concentrations were associated with poor response and absence of clinical benefit (nivolumab treatment less than 6 months). The variation of sPD-L1 concentrations were confirmed by RNA quantification. sPD-L1 concentrations were not correlated with PD-L1 expression on corresponding tumour samples. Low sGranB at nivolumab initiation was also associated with poor response. High sPD-L1 and low sGranB were associated with poor progression-free survival (PFS) and overall survival (OS). Low sPD-L2, low sIl-2 and high sIFN-γ were associated with grade 3-4 toxicities. Finally, miRNA screening showed that patients with clinical benefit (n = 9) had down-expression of miRNA-320b and -375 compared to patients with early progression at 2 months (n = 9). In conclusion, our results highlight the interest of circulating biomarkers in patients treated with nivolumab.

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Section: Discussionmentioning

confidence: 99%

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

et al. 2018

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“…miR-196b-5p overexpression has been reported in gastrointestinal cancer types, such as pancreatic (47), colorectal (41), and gastric (48). However, the molecular relationship between miR-196b-5p and HOXA10 is not clear.…”

Section: Discussionmentioning

confidence: 99%

Methylation of the HOXA10 Promoter Directs miR-196b-5p–Dependent Cell Proliferation and Invasion of Gastric Cancer Cells

Shao

Chen

Peng

et al. 2018

Molecular Cancer Research

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The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, the regulation and role of miR-196b-5p in gastric cancer was investigated. Quantitative real-time RT-PCR (qPCR) demonstrated that miR-196b-5p is significantly overexpressed in human gastric cancer tissues (P<0.01). In addition, it was determined that HOXA10, a homeobox family member and host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels (P<0.001). Quantitative pyrosequencing methylation analysis, demonstrated significantly lower levels of DNA methylation at the HOXA10 promoter in gastric cancer, as compared to non-neoplastic gastric mucosa specimens. 5-Aza-2′-deoxycytidine treatment confirmed that demethylation of HOXA10 promoter induces the expression of HOXA10 and miR-196b-5p in gastric cancer cell model systems. Using the Tff1-KO mouse model of gastric neoplasia, hypo-methylation and overexpression of HOXA10 and miR-196b-5p in gastric tumors was observed, as compared to normal gastric mucosa from Tff1-WT mice. Mechanistically, reconstitution of TFF1 in human gastric cancer cells lead to an increased HOXA10 promoter methylation with reduced expression of HOXA10 and miR-196b-5p. Functionally, miR-196b-5p reconstitution promoted human gastric cancer cell proliferation and invasion in vitro. In summary, the current data demonstrates overexpression of miR-196b-5p in gastric cancer and suggests that TFF1 plays an important role in suppressing the expression of miR-196b-5p by mediating DNA methylation of the HOXA10 promoter. Loss of TFF1 expression may promote proliferation and invasion of gastric cancer cells through induction of promoter hypo-methylation and expression of the HOXA10/miR-196b-5p axis.

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“…Glioma has high mortality, high recurrence rate, and low cure rate, because of its rapid growth and metastasis behaviour (6,7). miRNA dysregulation has been implicated in the occurrence and progression of many human cancers, such as bladder cancer (28), gastric cancer (29), hepatocellular carcinoma (30), colorectal cancer (31) and glioma (32). Thus, some specific miRNAs are potential therapeutic targets for cancer diagnosis, therapy and prognosis (33,34).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-342 inhibits the progression of glioma by directly targeting PAK4

Wang

et al. 2017

Oncology Reports

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Glioma is an extremely aggressive and lethal type of brain tumour that originates from glial cells. MicroRNA (miRNA) dysregulation has been implicated in the occurrence and progression of many human cancers, including glioma. Thus, some specific miRNAs are potential therapeutic targets for glioma diagnosis, therapy and prognosis. MicroRNA-342 (miR‑342) has been reported to be abnormally expressed in various types of cancer. However, the precise roles of miR‑342 in glioma remain unknown. The present study showed that miR‑342 is relatively downregulated in glioma tissues and cell lines compared with that in adjacent normal tissues and normal human astrocytes. We observed that low miR‑342 expression levels are correlated with advanced WHO grades and low KPS scores of glioma patients. In addition, the results of the functional assays demonstrated that miR‑342 overexpression inhibits the proliferation and invasion of glioma cells and induces apoptosis. Further investigation revealed that P21 activated kinases 4 (PAK4) is a direct target of miR‑342 in glioma. PAK4 was significantly upregulated in glioma tissues and inversely correlated with miR‑342 expression. Moreover, PAK4 knockdown can mimic the effects of miR‑342 on glioma cell proliferation, invasion and apoptosis. Notably, restoration of expression of PAK4 reversed the suppressive effects induced by the miR‑342 in the glioma cells. The upregulation of miR‑342 inactivated the AKT and ERK pathways in glioma. These findings may contribute to the understanding of the molecular mechanism underlying the carcinogenesis and progression of glioma, and to provide novel therapeutic target for the treatment of glioma patients.

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Dysregulation of MicroRNA-196b-5p and MicroRNA-375 in Gastric Cancer

Cited by 30 publications

References 51 publications

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

Methylation of the HOXA10 Promoter Directs miR-196b-5p–Dependent Cell Proliferation and Invasion of Gastric Cancer Cells

MicroRNA-342 inhibits the progression of glioma by directly targeting PAK4

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