The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway

Liu, Yawen; Wang, Dawei; Chen, Hui; Wang, Huizhi; Min, Jingyu; Chen, Jiaxi; Wu, Shuhui; Ni, Xiufan; Zhang, Youli; Gong, Aihua; Xu, Min

doi:10.1002/1878-0261.12836

Cited by 23 publications

(18 citation statements)

References 37 publications

(44 reference statements)

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“…Subsequently, nuclear Lin28B increases the expression of TET3 by inhibiting mature let-7i. The increased TET3 will activate Lin28B for maintaining the stemness of pancreatic cancer ( 20 ). Thus, KRAS maintains the stemness of pancreatic cancer cells through a unique Lin28B/let-7i/TET3 feedback loop.…”

Section: Positive Feedback Loopmentioning

confidence: 99%

The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer

Shen

Xie

et al. 2022

Front. Oncol.

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Pancreatic cancer is the leading cause of cancer-related deaths worldwide, with limited treatment options and low long-term survival rates. The complex and variable signal regulation networks are one of the important reasons why it is difficult for pancreatic cancer to develop precise targeted therapy drugs. Numerous studies have associated feedback loop regulation with the development and therapeutic response of cancers including pancreatic cancer. Therefore, we review researches on the role of feedback loops in the progression of pancreatic cancer, and summarize the connection between feedback loops and several signaling pathways in pancreatic cancer, as well as recent advances in the intervention of feedback loops in pancreatic cancer treatment, highlighting the potential of capitalizing on feedback loops modulation in targeted therapy for pancreatic cancer.

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Section: Positive Feedback Loopmentioning

confidence: 99%

The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer

Shen

Xie

et al. 2022

Front. Oncol.

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“…Specifically, Lin28A facilitates glioblastoma neurosphere formation through constitutively activating K-Ras and suppressing let-7b and let-7g [ 101 ]. In pancreatic cancer, K-Ras blocks let-7i maturation by phosphorylating Lin28B at S243 and promoting Lin28B nuclear translocation [ 102 ]. The dietary agents sulforaphane, quercetin and catechins inhibit CSC-like activities of pancreatic cancer cells through let-7a induction and K-Ras inhibition [ 103 ].…”

Section: Csc Regulatory Pathways Involving Let-7 Mirnasmentioning

confidence: 99%

The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness

Shen

Wicha

et al. 2021

Cells

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Cancer has long been viewed as a disease of normal development gone awry. Cancer stem-like cells (CSCs), also termed as tumor-initiating cells (TICs), are increasingly recognized as a critical tumor cell population that drives not only tumorigenesis but also cancer progression, treatment resistance and metastatic relapse. The let-7 family of microRNAs (miRNAs), first identified in C. elegans but functionally conserved from worms to human, constitutes an important class of regulators for diverse cellular functions ranging from cell proliferation, differentiation and pluripotency to cancer development and progression. Here, we review the current state of knowledge regarding the roles of let-7 miRNAs in regulating cancer stemness. We outline several key RNA-binding proteins, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) involved in the regulation of let-7 biogenesis, maturation and function. We then highlight key gene targets and signaling pathways that are regulated or mutually regulated by the let-7 family of miRNAs to modulate CSC characteristics in various types of cancer. We also summarize the existing evidence indicating distinct metabolic pathways regulated by the let-7 miRNAs to impact CSC self-renewal, differentiation and treatment resistance. Lastly, we review current preclinical studies and discuss the clinical implications for developing let-7-based replacement strategies as potential cancer therapeutics that can be delivered through different platforms to target CSCs and reduce/overcome treatment resistance when applied alone or in combination with current chemo/radiation or molecularly targeted therapies. By specifically targeting CSCs, these strategies have the potential to significantly improve the efficacy of cancer therapies.

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“…The let7 micro-RNA family is a barrier to stemness. It is downregulated in pancreatic cancer cells though the activity of KRAS, which activates LIN28B, an inhibitor of let7 [53]. Thus, these two programs of EMT and stemness are intertwined to facilitate cancer development and progression.…”

Section: Mutations Of P53 In Pancreatic Carcino-genesis: the Role Of Epithelial To Mes-enchymal Transition And Pluripotency In Pancreaticmentioning

confidence: 99%

Mutations of p53 associated with pancreatic cancer and therapeutic implications

Voutsadakis

2021

Ann Hepatobiliary Pancreat Surg

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Pancreatic adenocarcinoma is a malignancy with rising incidence and grim prognosis. Despite improvements in therapeutics for treating metastatic pancreatic cancer, this disease is invariably fatal with survival time less than a few years. New molecular understanding of the pathogenesis of pancreatic adenocarcinoma based on efforts led by The Cancer Genome Atlas and other groups has elucidated the landscape of this disease and started to produce therapeutic results, leading to the first introduction of targeted therapies for subsets of pancreatic cancers bearing specific molecular lesions such as BRCA mutations. These efforts have highlighted that subsets of pancreatic cancers are particularly sensitive to chemotherapy. The most common molecular lesions in pancreatic adenocarcinomas are mutations in an oncogene KRAS and the TP53 gene that encodes for tumor suppressor protein p53. This paper will review the landscape of pancreatic cancers, focusing on mutations of p53, a major tumor suppressor protein, in pancreatic cancers and possible therapeutic repercussions.

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The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway

Abstract: The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway.

Cited by 23 publications

References 37 publications

The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer

The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer

The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness

Mutations of p53 associated with pancreatic cancer and therapeutic implications

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