MicroRNA‐200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells

Lo, Wen-Liang; Yu, Cheng Chia; Chiou, Guang-Yuh; Chen, Yi Wei; Huang, Pin I.; Chien, Chian‐Shiu; Tseng, Ling Ming; Chu, Pen–Yuan; Lü, Kai; Chang, Kuo Wei; Kao, Shou Yen; Chiou, Shih Hwa

doi:10.1002/path.2826

Cited by 124 publications

(89 citation statements)

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“…2D and E). Recent reports suggest that OSCC possess the potential of cancer stem cell (CSC) or the tumor initiating cell-like properties, and presents characteristics of aggressive tumor (22,26). Based on these studies as well as our finding that let-7d level is low in metastatic OSCC patients, we further explored the relationship between let-7d and cancer stemness properties of OSCC.…”

Section: Silencing Let-7d Enhances Mesenchymal Stem-like and Chemo-mentioning

confidence: 99%

“…All samples were obtained with informed consent. The OSCC patient characteristics were described previously (22). The procedures and methods were as described previously (22).…”

Section: Methodsmentioning

confidence: 99%

“…OECM1 was obtained from the American Type Culture Collection (ATCC) and cultured as described previously (22). All samples were obtained with informed consent.…”

Section: Methodsmentioning

confidence: 99%

“…All reagents and protocols were from Applied Biosystems and detection was performed by using a 7900HT fast real-time PCR system using RNU6B as internal controls. miRNA specific qRT-PCR was done in triplicate and repeated three times on the ABI PRISM 7700 Sequence Detector system (Applied Biosystems) (22).…”

Section: Mirna Isolation and Mirna Quantitative Real-time Reversetranmentioning

confidence: 99%

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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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Section: Silencing Let-7d Enhances Mesenchymal Stem-like and Chemo-mentioning

confidence: 99%

“…All samples were obtained with informed consent. The OSCC patient characteristics were described previously (22). The procedures and methods were as described previously (22).…”

Section: Methodsmentioning

confidence: 99%

“…OECM1 was obtained from the American Type Culture Collection (ATCC) and cultured as described previously (22). All samples were obtained with informed consent.…”

Section: Methodsmentioning

confidence: 99%

Section: Mirna Isolation and Mirna Quantitative Real-time Reversetranmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2011

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“…Overexpressed miR200c downregulates oncogenes Snail and ZEB1 (zink finger E box) and Ncadherin, but upregulates vimentin and Ecadherin (consequentially inhibiting the liberation and intranuclear transfer of βcatenin). The EMT and metastatic movements of squamous carcinoma cells with upregulated miR200c were inhibited (85). ZEB1 is the master regulator of EMT (the other EMTinducer gene product proteins are Snail, Twist, Slug); microRNAs miR200abc downregulate ZEB1 (86).…”

Section: Cd25mentioning

confidence: 99%

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

Sinkovics

2011

Int J Oncol

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Abstract. In some inflammasomes tumor cells are generated. The internal environment of the inflammasome is conducive to the induction of malignant transformation. Epigenetic changes initiate this process. The subverted stromal connective tissue cells act to promote and sustain the process of malignant trans formation. In its early stages, the premalignant cells depend on paracrine circuitries for the reception of growth factors. The ligands are derived from the connective tissue, and the receptors are expressed on the recipient premalignant cells. The initial events are not a direct attack on the protooncogenes, and thus it may be entirely reversible. Epigenetic processes of hypermethylation of the genes at the promoters of tumor suppressor genes (to silence them), and deacetylation of the histones aimed at the promoters of protooncogenes (to activate them) are ongoing. A large number of short RNA sequences (interfering, micro, short hairpin, noncoding RNAs) silence tumor suppressor genes, by neutralizing their mRNAs. In a serial sequence oncogenes undergo amplifications, pointmutations, translocations and fusions. In its earliest stage, the process is reversible by demethylation of the silenced suppressor gene promoters (to reactivate them), or reacetylation of the histones of the oncogene promoters, thus deactivating them. The external administration of histone deacetylase inhibitors usually leads to the restoration of histone acetylation. In time, the uncorrected processes solidify into constitutive and irreversible gene mutations. Some of the pathogens inducing inflammations with consquential malignant transformation contain oncogenic gene sequences (papilloma viruses, EpsteinBarr virus, Kaposi's sarcomaassociated herpesvirus, hepatitis B and C viruses, Merkel cell polyoma virus, Helicobacter pylori, enterotoxigenic Bacteroides fragilis). These induced malignancies may be multifocal. Other pathogens are devoid of any known oncogenic genomic sequences (mycoplasma vavcarcinogenesis, chlamydia MALTlymphoma genesis). In these cases the host's inflammatory reactions induce the malignant transformation in serial sequences of gene alterations initiated by hypoxia and reactive oxygen and nitrogen species generation. Carcinogenic intrinsic inflammatory processes endogenously initiated without a pathogen are recognized. Chronic inflammatory processes signal the RNA/DNA complex. In response, the DNA may revert into its ancient primordial 'immortal' format, which the clinics recognize as 'oncogenesis'. The DNA remains the ultimate master of bioengineering in order to sustain life. A discussion on the most versatile and resistant primordial RNA/ DNA complex and the pre, proto, and unicellular world in which they coexisted is included. Contents1. Pathogens without oncogenic genomic sequences activating cellular oncogenes 2. The inflammasome 3. Tumor cell colonies generated in the inflammasomes 4. Pathogens with potentially oncogenic genomic sequences 5. Mechanisms of inflammatory carcinogenesis Pathogens without oncogenic...

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Surgical Margins in the Genomic Era

Wolf¹

2012

Arch Otolaryngol Head Neck Surg

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MicroRNA‐200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells

Cited by 124 publications

References 46 publications

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

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

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

Surgical Margins in the Genomic Era

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