Long non-coding RNA HOTAIR is associated with human cervical cancer progression

Kim, Hee Jung; Lee, Dae Woo; Yim, Ga Won; Nam, Eun Ji; Kim, Sung Hoon; Kim, Sang Wun; Kim, Young Tae

doi:10.3892/ijo.2014.2758

Cited by 182 publications

(174 citation statements)

References 41 publications

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“…In cervical cancer, many LncRNAs have been found to suppress metastasis, as well as help in the prediction of metastasis through their expression levels (15). HOX transcript antisense intergenic RNA (HOTAIR) has been identified as an upregulated LncRNA in cervical cancer (16), and a recent study has revealed that HOTAIR enhanced aggressive biological behavior and induced radio-resistance via inhibiting p21 in cervical cancer, which proposed that targeting HOTAIR might be a potent therapeutic strategy in cervical cancer, especially for those patients who were administered radiotherapy (17). However, little is known about the overall biological role of HOTAIR in cervical cancer, or the underlying molecular mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA HOTAIR modulates HLA-G expression by absorbing miR-148a in human cervical cancer

Sun

Chu

et al. 2016

International Journal of Oncology

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Abstract. The long non-coding RNA HOX transcript antisense RNA (HOTAIR) has been found overexpressed in many human malignancies and involved in tumor progression and metastasis. However, little is known about the potential biological roles of HOTAIR in tumor escape. In the present study, the expression of HOTAIR was detected in 59 paired cervical cancer tissue samples by real-time PCR and then subjected to correlation analysis with clinical features. The effects of HOTAIR on cervical cancer cells as well as the expression of human leukocyte antigen (HLA)-G were studied by overexpression and RNA interference approaches. Insight into the mechanism of HOTAIR acting as competitive endogenous RNAs (ceRNAs) was gained from bioinformatic analysis and luciferase assays. HOTAIR expression was obviously increased in cervical cancer tissue. HOTAIR upregulation was associated with advanced pathological stage, histology, lymph node invasion and lymphatic metastasis, and also correlated with shorter overall survival of cervical cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of cervical cancer cells, while HOTAIR knockdown inhibited cell invasion and cell viability, induced apoptosis and inhibited growth in vitro and in vivo. Moreover, HOTAIR modulated human leucocyte antigen-G (HLA-G) expression by competitively binding miR-148a. Our data suggest that HOTAIR plays an important oncogenic role in cervical cancer and might serve as a marker for cervical cancer prognosis and a potential target for therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

Long non-coding RNA HOTAIR modulates HLA-G expression by absorbing miR-148a in human cervical cancer

Sun

Chu

et al. 2016

International Journal of Oncology

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“…[85][86][87][88][89] HOTAIR expression supports metastasis in breast cancer and has been linked to poor outcome in several malignancies. 85 Padua Alves et al 86 examined breast and colon cancer cell lines in studies of HOTAIR regulation and found that this lncRNA was increased after TGFβ1 treatment in both breast and colon cancers.…”

Section: Hox Transcript Antisense Intergenic Rna (Hotair)mentioning

confidence: 99%

“…86 HOTAIR has also been implicated in the regulation of CSCs in cervical cancer and endometrial cancer. [87][88][89] LINC-ROR Linc-ROR was first discovered in induced pluripotent stem cells (iPSCs) where it was regulated by the key pluripotency factors Oct4, Sox2 and Nanog. 90 Linc-ROR has a principal role in maintenance of iPSCs and embryonic stem cells by preventing the activation of cellular stress pathways including the p53 response.…”

Section: Hox Transcript Antisense Intergenic Rna (Hotair)mentioning

confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

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The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

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“…Numerous studies revealed the potential role of lncRNAs molecules in cervical cancer progression, invasion and metastasis. For example, reports have shown that lncRNA HOTAIR is significantly overexpressed in cervical cancer and furthermore its expression is correlated with tumour progression and metastasis and can predict a poor prognosis in patients with cervical cancer 13, 27, 28. Another intensely studied lncRNAs in cervical oncogenesis is MALAT1 who was found to be highly expressed in cancer advances stages, shown to promote proliferation, growth and invasion and overall can predict a poor prognosis 29, 30.…”

Section: Discussionmentioning

confidence: 99%

LINC01101 and LINC00277 expression levels as novel factors in HPV‐induced cervical neoplasia

Iancu

Anton

Botezatu

et al. 2017

J Cellular Molecular Medi

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Recently long non‐coding RNAs were identified as new factors involved in gene expression regulation. To gain insight into expression pattern of these factors related to E7 HPV18 oncogene, this study uses HeLa cell culture transfected with E7‐siRNA. Gene expression profile was investigated using microarray analysis. After analysing the microarray results, we identified 15,387 RNA species differentially expressed in E7‐siRNA‐transfected cells compared with controls (fold change >2). The expression profiles of lncRNA species highlighted 731 lncRNAs and 203 lincRNAs. We selected two lincRNAs (LINC01101 and LINC00277) and we evaluated the expression profile in HPV‐induced neoplasia. Both lincRNAs investigated display a significantly reduced pattern of expression in cervical lesions and cancer, associated with clinical parameters. A connection between HPV presence and lincRNAs was noted. hrHPV‐positive samples exhibit significantly reduced LINC01101 and LINC00277 expression level (P < 0.05). These results provide new insights into involvement of lncRNA in HPV‐induced cervical cancer, enriching our understanding of their potential role in this pathology.

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Long non-coding RNA HOTAIR is associated with human cervical cancer progression

Cited by 182 publications

References 41 publications

Long non-coding RNA HOTAIR modulates HLA-G expression by absorbing miR-148a in human cervical cancer

Long non-coding RNA HOTAIR modulates HLA-G expression by absorbing miR-148a in human cervical cancer

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

LINC01101 and LINC00277 expression levels as novel factors in HPV‐induced cervical neoplasia

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