Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome

Liu, Mengjie; Guo, Hui; Jiao, Min; Wang, Shuhong; Tian, Tao; Fu, Xiao; Wang, Wen‐Juan

doi:10.2147/cmar.s298580

Cited by 5 publications

(4 citation statements)

References 36 publications

(29 reference statements)

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“…Likely, gene copy number, epigenetic alterations, and microenvironment-derived stimulant regulate PD-1 expression in human cancer cells. [32][33][34][35][36] As c-Fos binds to the AP-1-binding site and activates Pdcd1 transcription in tumor-infiltrating T cells, 29 Fos reduction was retrieved among the genes regulated in NIVO-treated colon cancer cells. Also, FOXO4 and FOXO3 were regulated by NIVO treatment in human colon cancer cells, mechanism previously reported for FOXO1 in antigen-specific CD8 +T cells during chronic lymphocytic choriomeningitis virus infection.…”

Section: Discussionmentioning

confidence: 99%

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

Ieranò

Righelli

D’Alterio

et al. 2022

J Immunother Cancer

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BackgroundColorectal cancer (CRC) is one of the most prevalent and deadly tumors worldwide. The majority of CRC is resistant to anti-programmed cell death-1 (PD-1)-based cancer immunotherapy, with approximately 15% with high-microsatellite instability, high tumor mutation burden, and intratumoral lymphocytic infiltration. Programmed death-ligand 1 (PD-L1)/PD-1 signaling was described in solid tumor cells. In melanoma, liver, and thyroid cancer cells, intrinsic PD-1 signaling activates oncogenic functions, while in lung cancer cells, it has a tumor suppressor effect. Our work aimed to evaluate the effects of the anti-PD-1 nivolumab (NIVO) on CRC cells.MethodsIn vitro NIVO-treated human colon cancer cells (HT29, HCT116, and LoVo) were evaluated for cell growth, chemo/radiotherapeutic sensitivity, apoptosis, and spheroid growth. Total RNA-seq was assessed in 6–24 hours NIVO-treated human colon cancer cells HT29 and HCT116 as compared with NIVO-treated PES43 human melanoma cells. In vivo mice carrying HT29 xenograft were intraperitoneally treated with NIVO, OXA (oxaliplatin), and NIVO+OXA, and the tumors were characterized for growth, apoptosis, and pERK1/2/pP38. Forty-eight human primary colon cancers were evaluated for PD-1 expression through immunohistochemistry.ResultsIn PD-1+ human colon cancer cells, intrinsic PD-1 signaling significantly decreased proliferation and promoted apoptosis. On the contrary, NIVO promoted proliferation, reduced apoptosis, and protected PD-1+ cells from chemo/radiotherapy. Transcriptional profile of NIVO-treated HT29 and HCT116 human colon cancer cells revealed downregulation of BATF2, DRAM1, FXYD3, IFIT3, MT-TN, and TNFRSF11A, and upregulation of CLK1, DCAF13, DNAJC2, MTHFD1L, PRPF3, PSMD7, and SCFD1; the opposite regulation was described in NIVO-treated human melanoma PES43 cells. Differentially expressed genes (DEGs) were significantly enriched for interferon pathway, innate immune, cytokine-mediated signaling pathways. In vivo, NIVO promoted HT29 tumor growth, thus reducing OXA efficacy as revealed through significant Ki-67 increase, pERK1/2 and pP38 increase, and apoptotic cell reduction. Eleven out of 48 primary human colon cancer biopsies expressed PD-1 (22.9%). PD-1 expression is significantly associated with lower pT stage.ConclusionsIn PD-1+ human colon cancer cells, NIVO activates tumor survival pathways and could protect tumor cells from conventional therapies.

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Section: Discussionmentioning

confidence: 99%

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

Ieranò

Righelli

D’Alterio

et al. 2022

J Immunother Cancer

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“…Mengjie Liu et al. performed an immunohistochemical staining study on colon cancer patient samples and revealed that high CXCL11 expression in colon cancer was associated with poor prognosis and could be used as a biomarker for prognosis ( 36 ). However, in terms of tumor progression Yingying Cao et al.…”

Section: Discussionmentioning

confidence: 99%

“…P53 was previously thought to inhibit cancer progression, and recent studies have found that he can promote cancer (34,35). Mengjie Liu et al performed an immunohistochemical staining study on colon cancer patient samples and revealed that high CXCL11 expression in colon cancer was associated with poor prognosis and could be used as a biomarker for prognosis (36). However, in terms of tumor progression Yingying Cao et al found that CXCL11 could promote anti-tumor immunity to prolong survival (37).…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA AL513318.2 as ceRNA Binding to hsa-miR-26a-5p Upregulates SLC6A8 Expression and Predicts Poor Prognosis in Non-Small Lung Cancer

Fan

Zhou

et al. 2022

Front. Oncol.

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BackgroundStudies have demonstrated that the regulatory role of competitive endogenous RNA (ceRNA) networks is closely related to tumorigenesis, which provides new targets for tumor therapy. In this study, the focus was to explore the ceRNA networks that regulate SLC6A8 expression and their prognosis in non-small cell lung cancer (NSCLC).MethodsFirstly, the Cancer Genome Atlas (TCGA) data combined with immunohistochemical staining was used to compare SLC6A8 expression in NSCLC tissues and normal tissues. Thereafter, samples from the immunohistochemical staining of NSCLC were integrated with clinical follow-up data for prognostic analysis. The Starbase database was employed to search for SLC6A8-targeted miRNAs and lncRNAs, and survival analysis was performed using clinical data from TCGA to obtain SLC6A8 expression and prognosis-related ceRNA networks. Finally, the prognostic and therapeutic prospects of SLC6A8 in NSCLC were further analyzed from methylation sites and the immune microenvironment.ResultsThe study results revealed that SLC6A8 was significantly overexpressed in NSCLC tissues compared to normal tissues, and clinical follow-up data showed that the overexpression group was associated with poor prognosis. In addition, the Starbase data combined with TCGA clinical data analysis demonstrated that the AL513318.2/hsa-miR-26a-5p/SLC6A8 network regulates SLC6A8 overexpression in NSCLC and is associated with poor prognosis. Methylation analysis revealed that 11 methylation sites were closely associated with the prognosis of NSCLC. In addition, the immune prognostic risk model showed that the high-risk group was associated with a poorer prognosis than the low-risk group, despite showing a better immunotherapy outcome.ConclusionIn summary, the AL513318.2/hsa-miR-26a-5p/SLC6A8 network upregulates SLC6A8 expression in NSCLC and is associated with poor prognosis. Therefore it may be a prognostic biomarker of NSCLC and a potential therapeutic target.

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“…In fact, it is now clear that RBPs are dysregulated in several types of cancer, thereby affecting the expression and function of oncoproteins and/or tumor suppressor proteins [ 7 , 8 ]. Clinicopathological and immunohistochemical studies of cancer cases have shown that some RBPs are abnormally expressed in cancer relative to the surrounding normal tissues, and such aberrant expression is correlated with the prognosis of patients [ 9 , 10 , 11 ]. For example, Wang et al identified RBM39 as a differentially expressed RBPs in acute myeloid leukemia (AML) compared with normal human CD34 + hematopoietic stem and progenitor cells [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Pathogenic Roles of RNA-Binding Proteins in Sarcomas

Kawachi

et al. 2022

Cancers

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RNA-binding proteins (RBPs) are proteins that physically and functionally bind to RNA to regulate the RNA metabolism such as alternative splicing, polyadenylation, transport, maintenance of stability, localization, and translation. There is accumulating evidence that dysregulated RBPs play an essential role in the pathogenesis of malignant tumors including a variety of types of sarcomas. On the other hand, prognosis of patients with sarcoma, especially with sarcoma in advanced stages, is very poor, and almost no effective standard treatment has been established for most of types of sarcomas so far, highlighting the urgent need for identifying novel therapeutic targets based on the deep understanding of pathogenesis. Therefore, defining the network of interactions between RBPs and disease-related RNA targets will contribute to a better understanding of sarcomagenesis and identification of a novel therapeutic target for sarcomas.

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Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome

Cited by 5 publications

References 36 publications

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

Long Non-Coding RNA AL513318.2 as ceRNA Binding to hsa-miR-26a-5p Upregulates SLC6A8 Expression and Predicts Poor Prognosis in Non-Small Lung Cancer

Pathogenic Roles of RNA-Binding Proteins in Sarcomas

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