TTC22 promotes m6A-mediated WTAP expression and colon cancer metastasis in an RPL4 binding-dependent pattern

You, A-Bin; Tian, Wei; Yuan, Hongfan; Gu, Lin; Zhou, Jing; Deng, Dajun

doi:10.1038/s41388-022-02402-x

Cited by 15 publications

(11 citation statements)

References 43 publications

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“…Our and others' works indicate that miR663a inhibits the development and metastasis of colon cancer and that miR663a target genes MALAT1 and TTC22 promote colon cancer metastasis [7,16,43,44] . Here, we further found that miR663AHG could inhibit the proliferation, migration/invasion of colon cancer cells in vitro and the growth and lung metastasis of colon cancer cells in vivo.…”

Section: Discussionsupporting

confidence: 53%

LncRNA miR663AHG represses the development of colon cancer in a miR663a expression-dependent negative feedback loop

Yuan

et al. 2022

Preprint

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Background The MIR663AHG gene encode both miR663AHG and miR663a. While miR663a contributes to the defense of host cells against inflammation and inhibits colon cancer development, the biological function of lncRNA miR663AHG has not been previously reported. Methods The subcellular localization of lncRNA miR663AHG was determined by RNA-FISH. miR663AHG and miR663a were measured by qRT-PCR. The effects of miR663AHG on the growth and metastasis of colon cancer cells were investigated in vitro and in vivo. CRISPR/Cas9, RNA pulldown, and other biological assays were used to explore the underlying mechanism of miR663AHG. Results miR663AHG was mainly distributed in the nucleus of Caco2 and HCT116 cells and the cytoplasm of SW480 cells. The expression level of miR663AHG was positively correlated with the level of miR663a (r = 0.179, P = 0.015) and significantly downregulated in colon cancer tissues relative to paired normal tissues from 119 patients (P < 0.008). Colon cancers with low miR663AHG expression were associated with advanced pTNM stage (P = 0.021), lymph metastasis (P = 0.041), and shorter overall survival (hazard ratio = 2.026; P = 0.021). Experimentally, miR663AHG inhibited colon cancer cell proliferation, migration, and invasion. The growth of xenografts from RKO cells overexpressing miR663AHG was slower than that of xenografts from vector control cells in BALB/c nude mice (P = 0.007). Interestingly, either RNA-interfering or resveratrol-inducing expression changes of miR663AHG or miR663a can trigger negative feedback regulation of transcription of the MIR663AHG gene. Mechanistically, miR663AHG could bind to miR663a and its precursor pre-miR663a, and prevent the degradation of miR663a target mRNAs. Disruption of the negative feedback by knockout of the MIR663AHG promoter, exon-1, and pri-miR663A-coding sequence entirely blocked these effects of miR663AHG. Conclusion miR663AHG functions as a tumor suppressor that inhibits the development of colon cancer through its cis-binding to miR663a/pre-miR663a. The negative feedback loop between miR663AHG and miR663a expression may play dominant roles in maintaining the functions of miR663AHG in colon cancer development.

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Section: Discussionsupporting

confidence: 53%

LncRNA miR663AHG represses the development of colon cancer in a miR663a expression-dependent negative feedback loop

Yuan

et al. 2022

Preprint

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“…The human colorectal cancer cell lines HCT116, SW480, and RKO were kindly provided by Dajun Deng, who originally purchased these cells from ATCC [13], and cultured in RPMI 1640 medium. The human colorectal cancer cell line LoVo and the mouse colorectal cancer cell line MC38 were purchased from the National Infrastructure of Cell Line Resource (Beijing, China), and maintained in DMEM medium.…”

Section: Materials and Methods Cell Culture And Transfectionmentioning

confidence: 99%

“…Western blotting analysis was performed as previously described [13]. In brief, cells were lysed with RIPA buffer containing protease and phosphatase inhibitors.…”

Section: Western Blotting Analysismentioning

confidence: 99%

CMTR1 promotes colorectal cancer cell growth and immune evasion by transcriptionally regulating STAT3

et al. 2023

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CMTR1, also called IFN-stimulated gene 95 kDa protein (ISG95), is elevated by viral infection in a variety of cells. However, the functions of CMTR1 in colorectal cancer (CRC), especially its roles in tumorigenesis and immune regulation, remain unclear. Here, we first identified CMTR1 as a novel oncogene in colorectal cancer. Based on The Cancer Genome Atlas (TCGA) database exploration and human tissue microarray (TMA) analysis, we found that CMTR1 expression was markedly higher in CRC tissues than in adjacent normal tissues. High CMTR1 expression was correlated with poor prognosis in CRC patients. Knockdown (KD) of CMTR1 significantly suppressed cell proliferation and tumorigenicity both in vitro and in vivo, whereas overexpression of CMTR1 resulted in the opposite effects. KEGG pathway analysis revealed differential enrichment in the JAK/STAT signaling pathway in colorectal cancer cells with CMTR1 KD. Mechanistically, suppression of CMTR1 expression inhibited RNAPII recruitment to the transcription start site (TSS) of STAT3 and suppressed STAT3 expression and activation. Furthermore, the efficacy of PD1 blockade immunotherapy was prominently enhanced in the presence of CMTR1 KD via increased infiltration of CD8 + T cells into the tumor microenvironment. Overall, it appears that CMTR1 plays a key role in regulating tumor cell proliferation and antitumor immunity.

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“…Wound healing assays. A total of 1.25x10 5 transfected PaTu8988 and PANC-1 cells/well were seeded for 24 h and cultured with DMEM (HyClone; Cytiva) only. Subsequently, a wound was created by scratching the monolayer of cells using a 10-µl plastic tip, nonadherent cells were washed away by PBS.…”

Section: Knockdown Of Gene Expression Using Sirnasmentioning

confidence: 99%

TTC22 as a potential prognostic marker and therapeutic target in pancreatic cancer: Insights into immune infiltration and epithelial‑mesenchymal transition

Ding,

Wang,

Cao

et al. 2023

Oncol Lett

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The mortality rate of pancreatic adenocarcinoma is high, and the effect of traditional treatment is unsatisfactory, thus novel biomarkers are required. Although the important role of tetratricopeptide repeat domain 22 (TTC22) in colon cancer is well established, its precise role in pancreatic cancer remains unclear and requires further investigation. Pan-cancer analysis and single-cell sequencing revealed TTC22 was differentially expressed in various tumors, especially in pancreatic adenocarcinoma. Additionally, clinical data for pancreatic cancer showed a negative association between TTC22 expression and clinical parameters, including survival prognosis. The correlation between TTC22 and immune infiltration in pancreatic cancer was validated by functional enrichment analysis. ESTIMATE and single sample Gene Set Enrichment Analysis algorithms were used to further analyze immune infiltration of TTC22 in pancreatic cancer, and the results suggested that TTC22 inhibited tumor immunity and was negatively correlated with plasmacytoid dendritic cells. Reverse transcription-quantitative PCR further confirmed the differential expression of TTC22 in pancreatic cancer cell lines. Wound healing, Transwell and colony formation assays showed that TTC22 affected the migration and invasion of pancreatic cancer cells. These findings demonstrate that TTC22 may serve as a potential prognostic marker and therapeutic target for the management of pancreatic cancer.

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TTC22 promotes m6A-mediated WTAP expression and colon cancer metastasis in an RPL4 binding-dependent pattern

Cited by 15 publications

References 43 publications

LncRNA miR663AHG represses the development of colon cancer in a miR663a expression-dependent negative feedback loop

LncRNA miR663AHG represses the development of colon cancer in a miR663a expression-dependent negative feedback loop

CMTR1 promotes colorectal cancer cell growth and immune evasion by transcriptionally regulating STAT3

TTC22 as a potential prognostic marker and therapeutic target in pancreatic cancer: Insights into immune infiltration and epithelial‑mesenchymal transition

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