The novel long noncoding RNA CRART16 confers cetuximab resistance in colorectal cancer cells by enhancing ERBB3 expression via miR-371a-5p

Zhang, Xiaoqian; Wen, Lin; Chen, Shanwen; Zhang, Junling; Ma, Yue; Hu, Jiayin; Yue, Taohua; Wang, Jingui; Zhu, Jing; Bu, Dingfang; Wang, Xin

doi:10.1186/s12935-020-1155-9

Cited by 31 publications

(35 citation statements)

References 48 publications

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“…Signi cantly upregulated and downregulated miRNAs were also identi ed, such as miR-371a-5p (logFC = 7.62, p < < 0.001) and miR-122-5p (logFC=-3.87, p < < 0.001). Previous studies have revealed that miR-371a-5p can affects the MAPK signaling pathway, which is closely related to cell apoptosis and lipid metabolism [51,52]. In contrast, the overexpression of miR-371a-5p can promote the proliferation and metastasis of cancer cells [53].…”

Section: Discussionmentioning

confidence: 99%

Differences in Genetics and Microenvironment of Lung Adenocarcinoma Patients with or without TP53 Mutation

Zeng

et al. 2021

Preprint

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Background: Differences in genetics and microenvironment of lung adenocarcinoma (LUAD) patients with or without TP53 mutation were analyzed to illustrate the role of TP53 mutation within the carcinogenesis of LUAD, which will provide new concepts for the treatment of LUAD.Methods: In this study, we used genetics and clinical info from the TCGA database, including somatic mutations data, RNA-seq, miRNA-seq, and clinical data. More than one bioinformatics tools were used to analyze the unique genomic pattern of TP53-related LUAD.Results: According to TP53 gene mutation status, we divided the LUAD patients into two groups, including 265 in the mutant group (MU) and 295 in the wild-type group (WT). 787 significant somatic mutations were detected between the groups, includingmutations in titin (TTN), type 2 ryanodine receptor (RYR2) and CUB and Sushi multiple domains 3(CSMD3), which were up-regulated in the MU. However, no significant survival difference was observed. At the RNA level, we obtained 923 significantly differentially expressed genes; in the MU, α-defensin 5(DEFA5),pregnancy-specific glycoprotein 5(PSG5) and neuropeptide Y(NPY) were the most up-regulated genes, glucose-6-phosphatase (G6PC), alpha-fetoprotein (AFP) and carry gametocidal (GC) were the most down-regulated genes. GSVA analysis revealed 30 significant pathways. Compared with the WT, the expression of 12 pathways in the mutant group was up-regulated, most of which pointed to cell division. There were significant differences in tumor immune infiltrating cells, such as Macrophages M1, T cells CD4 memory activated, Mast cells resting, and Dendritic cells resting. In terms of immune genes, a total of 35 immune-related genes were screened, of which VGF (VGF nerve growth factor inducible) and PGC (peroxisome proliferator-activated receptor gamma coactivator) were the most significant up-regulated and down-regulated genes, respectively. Research on the expression pattern of immunomodulators found that 9 immune checkpoint molecules and 6 immune costimulatory molecules were considerably wholly different between the two groups.Conclusion: Taking the mutant group as a reference, LUAD patients in the mutant group had significant differences in somatic mutations, mRNA-seq, miRNA-seq, immune infiltration, and immunomodulators, indicating that TP53 mutation plays a crucial role in the occurrence and development of LUAD.

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Section: Discussionmentioning

confidence: 99%

Differences in Genetics and Microenvironment of Lung Adenocarcinoma Patients with or without TP53 Mutation

Zeng

et al. 2021

Preprint

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“…Elevated expression of HER3, a member of the EGF receptor family, has been reported to play an essential role in cancer progression and correlates with worse overall survival in many solid tumors 1 , 2 . Additionally, a number of studies revealed the upregulation of HER3 as an important resistance mechanism upon EGFR and HER2-targeted therapy 3 – 5 , emphasizing the importance in developing novel therapeutic strategies targeting HER3. HER3 comprises an impaired tyrosine kinase domain and requires heterodimerization with and transphosphorylation by other members of the EGFR family for activation and signaling 1 .…”

Section: Introductionmentioning

confidence: 99%

A scDb-based trivalent bispecific antibody for T-cell-mediated killing of HER3-expressing cancer cells

Beha

Steinlein

Kühl

et al. 2021

Sci Rep

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HER3 is a member of the EGF receptor family and elevated expression is associated with cancer progression and therapy resistance. HER3-specific T-cell engagers might be a suitable treatment option to circumvent the limited efficacy observed for HER3-blocking antibodies in clinical trials. In this study, we developed bispecific antibodies for T-cell retargeting to HER3-expressing tumor cells, utilizing either a single-chain diabody format (scDb) with one binding site for HER3 and one for CD3 on T-cells or a trivalent bispecific scDb-scFv fusion protein exhibiting an additional binding site for HER3. The scDb-scFv showed increased binding to HER3-expressing cancer cell lines compared to the scDb and consequently more effective T-cell activation and T-cell proliferation. Furthermore, the bivalent binding mode of the scDb-scFv for HER3 translated into more potent T-cell mediated cancer cell killing, and allowed to discriminate between moderate and low HER3-expressing target cells. Thus, our study demonstrated the applicability of HER3 for T-cell retargeting with bispecific antibodies, even at moderate expression levels, and the increased potency of an avidity-mediated specificity gain, potentially resulting in a wider safety window of bispecific T-cell engaging antibodies targeting HER3.

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“…Colorectal cancer (CRC) is a prevalent malignancy of the digestive system. It is the third most common cancer worldwide and is ranked as the second cause of cancer‐related death 1,2 . Currently, surgical treatment, chemotherapy, and targeted therapy are the leading methods of CRC treatment and, with the continuous optimization of the treatment plan, the treatment effect continues to be improved 3 .…”

Section: Introductionmentioning

confidence: 99%

lncRNA MCM3AP‐AS1 inhibits the progression of colorectal cancer via the miR‐19a‐3p/FOXF2 axis

Dai

Zeng

Lee

2021

The Journal of Gene Medicine

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Background Long non‐coding RNA MCM3AP antisense RNA 1 (lncRNA MCM3AP‐AS1) has a regulatory role in the development of diverse malignancies, whereas its role and mechanism in colorectal cancer (CRC) is not yet clear. Methods The relative expression of MCM3AP‐AS1, miR‐19a‐3p and forkhead box F2 (FOXF2) mRNA in 53 cases of CRC and its adjacent normal tissues, human normal colonic mucosal cells (FHC cells) and CRC cell lines was examined by a quantitative real‐time polymerase chain reaction, and the changes of cell multiplication and migration were examined by the cell counting kit‐8 method, EdU test, and scratch‐healing test, respectively. Bioinformatics, dual‐luciferase reporter gene assay and a RNA immunoprecipitation experiment were adopted to predict and verify the relationship between MCM3AP‐AS1 and miR‐19a‐3p; bioinformatics and dual‐luciferase reporter gene assay were adopted to predict and verify the relationship between miR‐19a‐3p and FOXF2. Western blotting was executed to examine the effects of MCM3AP‐AS1 overexpression or knockdown on FOXF2 protein expression. Results MCM3AP‐AS1 expression was down‐modulated in CRC, and its dysregulation was linked to unfavorable pathological characteristics. MCM3AP‐AS1 significantly impeded the multiplication and migration of CRC cells. MCM3AP‐AS1 was recognized as a molecular sponge to suppress miR‐19a‐3p expression, and FOXF2 was a target gene of miR‐19a‐3p. MCM3AP‐AS1 positively modulated FOXF2 expression, and its biological effect was dependent the on miR‐19a‐3p/FOXF2 axis. Conclusions MCM3AP‐AS1 can inhibit CRC promoting by modulating the miR‐19a‐3p/FOXF2 axis.

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The novel long noncoding RNA CRART16 confers cetuximab resistance in colorectal cancer cells by enhancing ERBB3 expression via miR-371a-5p

Cited by 31 publications

References 48 publications

Differences in Genetics and Microenvironment of Lung Adenocarcinoma Patients with or without TP53 Mutation

Differences in Genetics and Microenvironment of Lung Adenocarcinoma Patients with or without TP53 Mutation

A scDb-based trivalent bispecific antibody for T-cell-mediated killing of HER3-expressing cancer cells

lncRNA MCM3AP‐AS1 inhibits the progression of colorectal cancer via the miR‐19a‐3p/FOXF2 axis

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