Chimeric RNA RRM2-C2orf48 plays an oncogenic role in the development of NNK-induced lung cancer

Zhou, Jiazhen; Guan, Xinchao; Xu, Enwu; Zhou, Jiaxin; Xiong, Rui; Yang, Qiaoyuan

doi:10.1016/j.isci.2022.105708

Cited by 4 publications

(1 citation statement)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, the high or low expression level of eight genes (IGF2BP3, PHF19, FUT11, C2orf48, IL1B, GPA33, PPP1R14C and UGT2B7) were associated with poor prognosis in CRC cohort. Of note, it has been reported that these genes were involved in tumor cell growth, proliferation, invasion and metastasis in various cancers [ 49 – 53 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer

Liu,

Zhou,

Liu

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the third most common cancer associated with a poor prognosis. Effective targeted therapy alone or in combination for treating advanced CRC remains to be a major clinical challenge. Here, we propose the therapeutic efficacy and molecular mechanism underlying RC48, a FDA-approved anti-HER2 antibody conjugate via a cleavable linker to the microtubule inhibitor monomethyl auristatin E (MMAE), either alone or in combination with gemcitabine (GEM) in various models of HER2-positive advanced CRC. Our findings demonstrated that HER2 was widely expressed and located on the plasma membrane of CRC patient specimens, PDX xenograft tumors and cell lines. It confirmed that RC48 alone significantly targeted and eradicated HER2 positive CRC tumor in these models. Moreover, we screened a panel of FDA-approved first-line chemotherapy drugs in vitro. We found that GEM exhibited stronger antiproliferative activity compared to the other first-line anti-cancer agents. Furthermore, combination therapy of RC48 and GEM significantly showed synergetic antitumor activity in vitro and in vivo. To gain further mechanistic insights into the combination therapy, we performed RNA-seq analysis. The results revealed that combination treatment of RC48 and GEM regulated multiple signaling pathways, such as PI3K-AKT, MAPK, p53, Foxo, apoptosis, cell cycle and cell senescence, etc., to exert its antitumor activity in CRC cells. Collectively, these preclinical findings demonstrated that RC48 alone or combinational therapy exerted promising antitumor activity, and meriting the preclinical framework for combinational therapy of anti-HER2 drug conjugate drug and chemotherapy drugs for HER2-positive patients with advanced CRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer

Liu,

Zhou,

Liu

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

show abstract

Oncogenic SLC2A11–MIF fusion protein interacts with polypyrimidine tract binding protein 1 to facilitate bladder cancer proliferation and metastasis by regulating mRNA stability

Cheng,

Yang,

et al. 2024

MedComm

View full text Add to dashboard Cite

Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2‐member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11–MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat‐Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11–MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11–MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half‐lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide‐3‐kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11–MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11–MIF mRNA is regulated by CCCTC‐binding factor and stabilized through RNA N4‐acetylcytidine modification facilitated by N‐acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11–MIF–PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.

show abstract

Hypermethylation of the ADIRF promoter regulates its expression level and is involved in NNK-induced malignant transformation of lung bronchial epithelial cells

Xiong,

Du,

Chen

et al. 2023

Arch Toxicol

View full text Add to dashboard Cite

Chimeric RNA RRM2-C2orf48 plays an oncogenic role in the development of NNK-induced lung cancer

Cited by 4 publications

References 46 publications

Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer

Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer

Oncogenic SLC2A11–MIF fusion protein interacts with polypyrimidine tract binding protein 1 to facilitate bladder cancer proliferation and metastasis by regulating mRNA stability

Hypermethylation of the ADIRF promoter regulates its expression level and is involved in NNK-induced malignant transformation of lung bronchial epithelial cells

Contact Info

Product

Resources

About