A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers

Christensen, Brock C.; Moyer, Benjamin J.; Avissar, Michele; Ouellet, Lauren G.; Plaza, Silvia Leonor Olivera; McClean, Michael D.; Marsit, Carmen J.; Kelsey, Karl T.

doi:10.1093/carcin/bgp099

Cited by 179 publications

(156 citation statements)

References 22 publications

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“…A number of experimental investigations have shown the tumor growth suppression effect of the Let-7 Let-7 and KRAS in colorectal cancer miRNA. [8][9][10][20][21][22] Therefore, it is not surprising that in vivo, Let-7 and Let-7 regulators may show an effect on clinical outcomes as recently found in patients with oral 13 and lung cancer. 23 Notably, the influence of the LCS6 variant on PFS and OS was present in the 55 unresponsive patients who were carriers of a KRAS mutation.…”

Section: Let-7 and Kras In Colorectal Cancermentioning

confidence: 84%

See 1 more Smart Citation

Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab–irinotecan

et al. 2010

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Section: Let-7 and Kras In Colorectal Cancermentioning

confidence: 84%

“…12 Patients with oral cancer showed adverse survival in the presence of the LCS6 G allele. 13 The KRAS 3 0 -UTR LCS6 single-nucleotide polymorphism has not been studied in colorectal carcinomas so far. Clinical investigations on this genetic feature may shed light on the influence of the Let-7 post-transcriptional control on KRAS in vivo.…”

Section: Introductionmentioning

confidence: 99%

Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab–irinotecan

et al. 2010

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“…Patients carrying the G allele live longer than those with the T allele. Researchers found that such functional SNPs are closely related to breast cancer risk , epithelial ovarian cancer risk (Pharoah et al, 2011), and prognosis of oral cancer (Christensen et al, 2009), among others.…”

Section: Discussionmentioning

confidence: 99%

A single nucleotide polymorphism in the promoter region of let-7 family is associated with lung cancer risk in Chinese

et al. 2015

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ABSTRACT. Lung cancer is a complex polygenic disease and many genetic factors are involved in the development of the disease. As one of the most important and widely studied families of microRNA, let-7 appears to play an important role in initiation and progression of lung cancer. Any small changes in miRNA level or its target point can cause significant changes in gene function. In this study, we examined whether a single-nucleotide polymorphism in the promoter region of the let-7 family (rs10877887) is associated with the susceptibility to L.Q. Shen et al. 4506©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 4505-4512 (2015) and prognosis of lung adenocarcinoma cancer. A hospital-based casecontrol research model was used in our study. The single-nucleotide polymorphism was genotyped in 69 lung cancer patients and 75 healthy controls by direct sequencing. The correlation between rs10877887 genotypes and the susceptibility to lung cancer was evaluated using an unconditional logistic regression model. Populations with the CT+CC genotype had a significantly increased AC risk compared to those with the TT genotype (CT+CC vs TT: P = 0.043, OR = 2.032, 95%CI = 1.018-4.054). Furthermore, the risk effect was greater in subgroups of females over 60 years old (CT+CC vs TT: OR = 6.857, 95%CI = 1.425-33.008, P = 0.012), and the C allele were confirmed to be a risk factor related to lung cancer in these females (P = 0.012). The singlenucleotide polymorphism rs10877887 in the promoter region of the let-7 family was found to be responsible for the susceptibility to lung adenocarcinoma cancer in Chinese individuals. This association was significantly stronger in females who were more than 60 years old.

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“…Let-7 has also been shown to act as a tumor suppressor, most likely through targeting a number of genes with oncogenic activity such as RAS (5)(6)(7)(8) or high mobility group (HMG) A2 (9,(37)(38)(39). Christensen et al found that the polymorphism of the let-7 biding site (KRAS-LCS6) is associated with reduced survival in oral cancer patients (40). The research group of the University of Florida also discovered that the Dicer, an RNase III endonuclease required for miRNA maturation, is overexpressed in oral cancers due to downregulation of let-7b (41).…”

Section: Discussionmentioning

confidence: 99%

Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer

et al. 2011

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Abstract. Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide. Let-7 family has been shown to function as a tumor suppressor through regulating multiple oncogenic signaling. Recent study reported that combined underexpression of miR-205 and let-7d showed negative correlation with the survival prognosis of head and neck cancer patients. However, the let-7d-involved mechanism in regulating OSCC is still unclear. In this study, we first demonstrated that let-7d expression was significantly decreased while Twist and Snail expression was increased in OSCC cancer cell lines and primary cultures as compared to normal human oral keratinocyte cells. To further investigate the role of let-7d in OSCC, we applied the SPONGE method to knock down let-7d in OECM-1 and two primary OSCC cell types. The results showed that knockdown of let-7d promote epithelialmesenchymal transition (EMT) traits and migratory/invasive capabilities in OSCC cells. Furthermore, down-expression of let-7d significantly activated Twist and Snail expressions and chemo-resistant abilities of OSCC cells. Notably, overexpression of let-7d effectively reversed the EMT phenotype, blocked migratory/invasive abilities, and further increased the chemosensitivity in oral cancer tumor initiating ALDH1 + cells. In sum, these results show that let-7d negatively modulates EMT expression and also plays a role in regulating chemo-resistant ability in oral cancer. IntroductionHead and neck squamous cell carcinoma, including oral squamous cell carcinoma (OSCC), is the sixth most prevalent malignancy worldwide and accounts for approximately 8-10% of all cancers in Southeast Asia (1,2). The prognosis of OSCC remains dismal as more than 50% of the patients die of this disease or complications within 5 years under current therapies (2). To increase patient survival rate, investigations elucidating the mechanisms of tumorigenesis in OSCC are urgently needed (2). Some studies have suggested that subsets of cancer stem cells (CSC) or tumor initiating cells (TICs) are responsible for tumor progression as well as recurrence after conventional chemotherapy (3). However, there is lack of suitable markers for isolating the crucial subset of tumor cells that is capable of reforming new tumors in vivo and accounts for tumor relapse in OSCC, according to CSC hypothesis of tumorigenesis.MicroRNAs (miRNAs), highly conserved small RNA molecules that regulate gene expression, can act as cancer signatures, oncogenes or tumor suppressors (4). The ubiquitously expressed let-7/miR-98 family was one of the first mammalian miRNAs to be identified (5-8). Let-7 family members have been described as being down-regulated during cancer progression in various human cancers including lung, gastric, ovarian, colon cancer, leiomyoma and melanoma (5-13). Let-7d, a member of the let-7 family of miRNAs, has also been shown to act as tumor suppressor, most likely through targeting RAS (14) or high mobility group A2 (15). Let-7d regulates senescence of human cord blood-derived multipotent ste...

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A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers

Cited by 179 publications

References 22 publications

Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab–irinotecan

Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab–irinotecan

A single nucleotide polymorphism in the promoter region of let-7 family is associated with lung cancer risk in Chinese

Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer

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