microRNA-375 inhibits colorectal cancer cells proliferation by downregulating JAK2/STAT3 and MAP3K8/ERK signaling pathways

Wei, Ran; Yang, Qin; Han, Bing; Li, Yan; Yao, Kun; Yang, Xiuyu; Chen, Zexi; Yang, Shanshan; Zhou, Jiaqi; Li, Meizhang; Yu, Hua; Yu, Min; Cui, Qinghua

doi:10.18632/oncotarget.15114

Cited by 51 publications

(33 citation statements)

References 25 publications

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“…43,44,60 Interestingly, miRNA-375 is strongly associated with the Wnt/ b-catenine pathway 49 and the Hippo pathway, 59,[61][62][63] known to be involved in ICIs resistance. [64][65][66][67][68][69][70] Moreover, miRNA-375 targets the JAK2 gene, 62,71 involved in the IFN-g and TNF-a pathways, key-regulators of cytotoxic CD8C immune response. 72 Taken together, these data, highlighted by our results, suggest an implication of both miRNA-320b and miRNA-375 in anti-tumour immune response with ICIs, and the potential utility of screening for these miRNA in plasma before beginning nivolumab to select patients who will have response and clinical benefit with this treatment.…”

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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“…Positive p-STAT3 expression in cervical cancer was associated with lymph node metastasis (17). Both miR-375 and miR-133b suppressed cell growth through the regulation of STAT3 signalling (18,19). All of these findings suggest that the biological behaviour of tumour cells may be regulated by STAT3 signalling activity.…”

Section: Introductionmentioning

confidence: 91%

LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma

et al. 2017

Oncol Rep

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La-related protein 1 (LARP1) is a conserved RNA-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Dysregulated LARP1 has been reported to be related to the development of several cancers. However, the exact function and mechanism of LARP1 in non-small cell lung cancer (NSCLC) is largely unknown. In the present study, we found that the mRNA levels of LARP1 were increased in NSCLC cells compared to those in normal control cells. Knockdown of LARP1 inhibited cell proliferation, migration and invasion in NSCLC cells and tumourigenicity in H520 cells. Both in vitro and in vivo analyses confirmed that STAT3 signalling was inactivated by the knockdown of LARP1. Moreover, LARP1 was identified as a direct target of miR-374a. Overexpression of miR-374a attenuated the promotor effects of LARP1 by inhibiting proliferation, metastasis and STAT3 signalling. Clinically, LARP1 was markedly overexpressed in NSCLC tissues, and upregulated LARP1 was correlated with tumour progression and poor survival. The expression of miR-374a was negatively correlated with the expression of LARP1 in NSCLC tissues. Furthermore, we found that XIST functioned as a competing endogenous RNA to suppress miR-374a, which regulated its downstream target LARP1. In summary, we suggest that the dysfunction of the XIST/miR-374a/LARP1 axis contributes to NSCLC and may serve as a promising therapeutic strategy for treatment.

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“…Dysregulated JAK2 influences the proliferation and aggression of lung adenocarcinoma cells . To our best knowledge, dysregulation of JAK2 in several cancer types, such as colorectal cancer, gastric cancer and thyroid cancer, is mainly caused by the up‐ or downregulation of upstream miR‐375 . However, whether the JAK2 expression in HCC is also mediated by miR‐375 remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Cao

Wang

et al. 2018

Immunol Cell Biol

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In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT‐PCR along with the low expression of its downstream miRNA miR‐375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR‐375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR‐375 by RNA pull‐down and dual‐luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR‐375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR‐375 and upregulating JAK2.

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microRNA-375 inhibits colorectal cancer cells proliferation by downregulating JAK2/STAT3 and MAP3K8/ERK signaling pathways

Cited by 51 publications

References 25 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

LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

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