LIN28B Promotes Colon Cancer Migration and Recurrence

Pang, Ming; Wu, Gang; Hou, Xiaolin; Hou, Nengyi; Liang, Liqin; Ge, Jia; Shuai, Ping; Luo, Bin; Wang, Kang; Li, Guoxin

doi:10.1371/journal.pone.0109169

Cited by 35 publications

(35 citation statements)

References 25 publications

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“…Furthermore, we analyzed the largest cohort of human CRC samples to date and observed that LIN28A and/or LIN28B expression correlated with invasive tumor pathology and poor prognosis, phenotypes accurately reflected in our murine model. While prior murine models have used LIN28B exclusively (King et al 2011a,b;Madison et al 2013;Pang et al 2014), we demonstrated an equally potent role of LIN28A in tumorigenesis and progression in both our murine model and human CRC. Our models illuminate several novel aspects of LIN28-induced tumor biology.…”

Section: Discussionmentioning

confidence: 40%

LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

Schwitalla

Qian

et al. 2015

Genes Dev.

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Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in Apc Min/+ mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target.

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Section: Discussionmentioning

confidence: 40%

LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

Schwitalla

Qian

et al. 2015

Genes Dev.

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“…For instance, several studies showed that Lin28B is overexpressed in colon cancer and promotes colon cancer progression [8, 9], whereas the expression and functions of Lin28A in colon cancer are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the expression and function of Lin28A and Lin28B in colon cancer

Wang

Zhu

et al. 2016

Oncotarget

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Lin28A and Lin28B are highly conserved RNA binding proteins with similar structure and functions. Recent studies demonstrated that both of them act as oncogenes and promote cancer progression. However, few researches compared the expression and functions of both oncogenes in human malignant tumors at same time. Additionally, although the expression and role of Lin28B in colon cancer is frequently reported, the expression and functions of Lin28A in colon cancer are largely unknown. In this study, we have systematically evaluated the expressional pattern, mutation status and correlation of both Lin28A and Lin28B in colon cancer tissues for the first time, and compared the roles of Lin28A and Lin28B in the proliferation, migration, invasion and apoptosis of colon cancer cells in vitro. We have showed that they are co-expressed and have functional similarities, however, the molecular mechanisms underlying their similar functions may not be identical. This study contributes to clarify the similarities and differences of Lin28A and Lin28B in colon cancer progression.

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“…Moreover, this variant was also found to be associated with the risk and survival of cancer, such as epithelial ovarian cancer [32], colon cancer [33,34], non-small cell lung cancer [35], oral cavity cancer [36], and neuroblastoma [16]. LIN28B protein was found to be unregulated in colon tumours, and the overexpression correlated with reduced patient survival and increased probability of tumour recurrence [34,37]; besides, LIN28B can promote migration, invasion, and malignant transformation of cells [38]. Furthermore, studies also found that the overexpression of LIN28B was associated with poor prognosis in head and neck cancer [39], oral squamous cell carcinoma patients [40,41], gastric cancer [42], breast cancer [43], ovarian cancer [44], and neuroblastoma [16,45,46].…”

Section: Discussionmentioning

confidence: 99%

Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children

Yang

Zhang

et al. 2016

J Cellular Molecular Medi

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Neuroblastoma is the most commonly diagnosed solid tumour outside the central nervous system in children. However, genetic factors underlying neuroblastoma remain largely unclear. Previous genome‐wide association study indicated that lin‐28 homolog B (LIN28B) might play an important role in the development of neuroblastoma and also contributed to its poor overall survival. With the purpose to evaluate the association between LIN28B gene polymorphisms and neuroblastoma susceptibility in Southern Chinese population, we conducted this study with 256 neuroblastoma cases and 531 cancer‐free controls. Four potentially functional polymorphisms (rs221634 A>T, rs221635 T>C, rs314276 C>A and rs9404590 T>G) were genotyped using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the associations between the selected single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We also performed genotype‐phenotype association analysis to explore the effects of the selected SNPs on LIN28B gene transcripts. Our results indicated that the rs221634 TT genotype was associated with an increased neuroblastoma risk (TT versus AA/AT: adjusted OR = 1.50, 95% CI = 1.04–2.17). The association was more pronounced in males, patients with tumour of mediastinum origin, as well as patients in early clinical stages. Moreover, overall analysis and stratified analysis also showed an increased risk of neuroblastoma for carrier of the 2–4 risk genotypes. In summary, these results indicated that the LIN28B rs221634 A>T polymorphism was associated with an increased neuroblastoma risk in Southern Chinese children. These findings need further validation in large studies with different ethnicities involved.

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LIN28B Promotes Colon Cancer Migration and Recurrence

Cited by 35 publications

References 25 publications

LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

Comparison of the expression and function of Lin28A and Lin28B in colon cancer

Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children

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