MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais

Lian, Sen; Xia, Yong; Nguyen, Thi Phuong; Joο, Young Eun; Kim, Kyung Keun; Kim, Hark Kyun; Jung, Young Do

doi:10.3390/ijms17101633

Cited by 20 publications

(16 citation statements)

References 52 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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“…GC is reported to be closely associated with the abnormal expression of miRNAs, including miR-375, miR-215 and miR-106a (24–26). Various miRNAs have been identified as important regulators of tumorigenesis and cancer progression through diverse molecular pathways (27).…”

Section: Discussionmentioning

confidence: 99%

miR-320a serves as a negative regulator in the progression of gastric cancer by targeting RAB14

Liu

Shao

et al. 2017

Molecular Medicine Reports

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Gastric cancer (GC) is one of the most common types of malignancy worldwide, with high morbidity and mortality rates. The dysregulation of microRNAs (miRs) has been found to be involved in the carcinogenesis of GC. The present study aimed to investigate the underlying association between GC and miR-320a. Analysis using reverse transcription quantitative polymerase chain reaction indicated that the expression of miR-320a was downregulated and the expression of RAB14 was upregulated in GC tissues and cells, compared with the corresponding controls. MTT, colony formation assays, and flow cytometric analyses were used to evaluate the effect of miR-320a on cell proliferation and the cell cycle. The ectopic expression of miR-320a using miR-320a mimics suppressed cell viability, inhibited G1/S transition, and induced apoptosis in AGS and MKN45 cells. In addition, RAB14 was identified as a direct target gene of miR-320a, according to the results of bioinformatics analysis and a luciferase reporter assay. Downregulation of RAB14 by RAB14-small interfering RNA inhibited the viability of GC cells, which was similar to the phenotype of miR-320a mimics. Furthermore, the reintroduction of RAB14 partially abrogated the miR-320a-mediated downregulation of RAB14 and rescued the miR-320a-induced effects on GC cell growth. These findings suggest a potential novel therapeutic target for the treatment of GC.

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“…For example, Lian’ et al reported that miR-375 functions as a tumor-suppressor gene in gastric cancer by targeting recepteur d’Origine Nantais [20]. Xu and his colleagues showed that miR-375 suppresses human colorectal cancer metastasis by directly acting upon Frizzled 8, suggesting that this miRNA may serve as a new therapeutic target to inhibit colorectal cancer metastasis [21].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-375 Inhibits Growth and Enhances Radiosensitivity in Oral Squamous Cell Carcinoma by Targeting Insulin Like Growth Factor 1 Receptor

Zhang

Hou

et al. 2017

Cell Physiol Biochem

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Background: MicroRNAs (miRNAs) have emerged as key players in various human biological processes, including tumorigenesis. Here, we investigated the roles of miR-375 in the pathogenesis of oral squamous cell carcinoma (OSCC). Methods: We performed quantitative real-time PCR (qRT-PCR) to detect miR-375 expression in OSCC tissues and corresponding normal oral epithelial tissues and analyze the correlation of miR-375 expression with OSCC metastasis and patient’s survival. Then, the effects of miR-375 expression on proliferation, cell cycle, apoptosis and radiosensitivity in OSCC cells were determined by using MTT, flow cytometry and clonogenic survival assays. A dual-luciferase reporter assay was performed to test whether miR-375 binds to the 3’-untranslated region (3’-UTR) of target mRNA. Results: The expression level of miR-375 in OSCC tissues was significantly lower than that in normal oral epithelial tissues, and low miR-375 expression was correlated with higher incidence of lymph node metastasis and poor survival of OSCC patients. Upregulation of miR-375 significantly inhibits growth, induces cell cycle arrest in G₀/G₁ phase, increases apoptosis and enhances radiosensitivity in OSCC cells. Analysis of luciferase activity demonstrated that miR-375 binds to the 3’-UTR of insulin like growth factor 1 receptor (IGF-1R). Small interfering RNA (shRNA)-mediated IGF-1R knockdown mimics the effects of miR-375 upregulation, while overexpression of IGF-1R partially reverses those effects in OSCC cells. Conclusion: It was obviously demonstrated that miRNA-375 inhibits growth and enhances radiosensitivity in OSCC cells by targeting IGF-1R, suggesting that miR-375 may be a potential therapeutic target for OSCC patients.

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MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais

Cited by 20 publications

References 52 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

miR-320a serves as a negative regulator in the progression of gastric cancer by targeting RAB14

MicroRNA-375 Inhibits Growth and Enhances Radiosensitivity in Oral Squamous Cell Carcinoma by Targeting Insulin Like Growth Factor 1 Receptor

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