Genetic variants in let-7/Lin28 modulate the risk of oral cavity cancer in a Chinese Han Population

Yu, Zhuang; Zhu, Lucheng; Wang, Ruixia; Miao, Limin; Jiang, Hongbing; Yuan, Hua; Ma, Hongxia; Chen, Ning

doi:10.1038/srep07434

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…Accumulating evidence has revealed essential clues regarding LIN28B expression and potential roles in oral cancers [ 19 , 20 ]. We have revealed a functional single nucleotide polymorphism [variant allele (T) of rs221636] in LIN28B,which is significantly associated with oral cancer susceptibility in a Chinese population, thus supporting the key roles of LIN28B during oral tumorigenesis [ 21 ]. However, the expression pattern of LIN28B and its clinicopathological significance in OSCC have not been definitively established yet.…”

Section: Introductionmentioning

confidence: 86%

The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis

et al. 2015

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ObjectiveLIN28B is a conserved RNA-binding protein critically involved in development, cellular metabolism and tumorigenesis. It is frequently overexpressed in human cancers and correlates with tumor aggressiveness as well as unfavorable prognosis. However, the expression pattern and oncogenic roles of LIN28B during oral squamous cell carcinoma (OSCC) development and progression has not been well established yet. Here, we sought to determine the expression of LIN28B and its clinical significance using chemical-induced OSCC animal model, cell lines and primary specimens.MethodThe OSCC animal model was induced using 7,12-dimethyl-1,2-bezan-tracene (DMBA) painting in the hamster buccal pouch. Buccal lesions from animals were obtained from different time points and subjected to routine histological analyses and immunohistochemical staining of LIN28B. The mRNA, protein abundance and subcellular localization of LIN28B was determined in a panel of OSCC cell lines by real-time RT-PCR, western blot and immunofluorescence. The expression levels of LIN28B in human primary OSCC samples were further evaluated by immunohistochemical staining. Moreover, the relationship between LIN28B and several clinicopathological parameters as well as patients’ prognosis were also assessed.ResultsOur results revealed that negative or low LIN28B expression was commonly observed in normal epithelial, whereas more LIN28B abundance was identified in epithelial dysplasia and invasive SCC in the DMBA-induced OSCC animal model. Overexpression of LIN28B was identified in a major fraction of OSCC samples(39/58) and significantly associated with tumor size (P = 0.049) and advanced clinical stages (P = 0.0286). Patients with increased LIN28B had markedly reduced overall survival as compared to those with low LIN28B. Multivariate survival analyses further indicated that LIN28B abundance served as an independent prognostic factor for patients’ overall survival.ConclusionsOur findings reveal that LIN28B is critically involved in OSCC initiation and progression and aberrantly overexpressed in human OSCC. It might represent a novel diagnostic and prognostic biomarker for oral cancer.

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Section: Introductionmentioning

confidence: 86%

The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis

et al. 2015

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“…In a study conducted in China, Zhang et al explored association between six genetic variants in let‐7/Lin28 and oral cavity cancer risk with 384 cases and 731 controls, and they detected a protective effect of LIN28B rs221636 on oral cavity cancer. However, they failed to observe the association with the risk of oral cavity cancer for LIN28A rs4659441 and rs3811463 . Sung et al conducted a two genome‐wide association study in East Asian with 5066 breast cancer cases and 4337 controls involving Koreans and Chinese.…”

Section: Discussionmentioning

confidence: 99%

LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four‐centre case‐control study

Zhang

Liu

et al. 2019

J Cellular Molecular Medi

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Wilms tumour is a renal malignancy that commonly occurs in children. LIN28A gene overexpression has been reported to be involved in various human malignancies, while its roles in Wilms tumour risk are still under investigation. Here, we genotyped four LIN28A polymorphisms in 355 Wilms tumour patients and 1070 healthy controls from four hospitals in China. The genotyped single nucleotide polymorphisms (SNPs) include the following: rs3811464 G>A, rs3811463 T>C, rs34787247 G>A and rs11247957 G>A. Overall, we found that rs3811463 T>C and rs34787247 G>A were associated with increased risk of Wilms tumour. Combination analysis of risk genotypes showed that, compared to non‐carriers, subjects with 1 risk genotype and 1‐3 risk genotypes were more likely to develop Wilms tumour, with an adjusted odds ratio (OR) of 1.58 and 1.56, respectively. Stratified analysis further demonstrated that the risk effect remained prominent in some subgroups. We also found that presence of 1‐3 risk genotypes was associated with Wilms tumour risk in subgroups > 18 months of age, females, males and those with clinical stage I + II diseases. Furthermore, expression quantitative trait locus (eQTL) analysis indicated that rs3811463 C allele was significantly associated with increased transcripts of LIN28A gene. These findings suggest that LIN28A gene polymorphisms may be associated with increased predisposition to Wilms tumour.

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“…Interestingly, later studies indicated that LIN28B rs314276 C>A polymorphism, which is included in our current study, is associated with timing of puberty [27], growth in height from birth to adulthood [28], finger-length ratio [29], growth in height from birth to adulthood [28], childhood obesity and age at menarche [30], and central precocious puberty and early puberty in girls [31]. 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].…”

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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Genetic variants in let-7/Lin28 modulate the risk of oral cavity cancer in a Chinese Han Population

Cited by 16 publications

References 34 publications

The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis

The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis

LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four‐centre case‐control study

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

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