MicroRNAs (miRNAs) are non-coding small RNAs that regulate cell proliferation and functions by interfering with the translation of target mRNAs. Altered expression of miRNA is known to induce various human malignancies. We examined the expression of miRNAs in squamous cell carcinoma of human head and neck (HNSCC) and esophagus (ESCC), compared to that in normal squamous epithelia as well as malignancies of other organs. Microarray analysis showed up-regulation of miR-21, miR-16 and miR-30a-5p in HNSCC and ESCC cell lines compared to normal squamous epithelial cell lines, and consistent high expression of miR-205 and let-7a in both normal and malignant squamous epithelial cell lines. Validation study using real-time quantitative RT-PCR in formalin-fixed paraffin-embedded cancer tissues and paired normal epithelia obtained by Laser-captured microdissection revealed that miR-205 showed highest expression in both malignant and benign squamous epithelia, although it was less expressed in cell lines and tissues other than squamous epithelia. MiR-21, which is an oncogenic miRNA in various malignancies, was also up-regulated in HNSCC and ESCC compared to paired normal squamous epithelia. These results suggest that miR-205 might be a specific marker miRNA of both normal and malignant squamous epithelia, while miR-21 might be a putative oncogenic miRNA in HNSCC and ESCC.
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http://dx.doi.org/10.3892/or_00000804 | DOI Listing |
While the genetic paradigm of cancer etiology has proven powerful, it remains incomplete as evidenced by the widening spectrum of non-cancer cell-autonomous "hallmarks" of cancer. Studies have demonstrated the commonplace presence of high oncogenic mutational burdens in homeostatically-stable epithelia. Hence, the presence of driver mutations alone does not result in cancer.
View Article and Find Full Text PDFbioRxiv
December 2024
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
AIDS Res Hum Retroviruses
December 2024
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
During male-to-female transmission, HIV-1 must cross the mucosal epithelium of the female reproductive tract to gain access to underlying target cells. Previously, we demonstrated that HIV-1 can penetrate intact columnar and squamous genital epithelia in both and systems. We found that the virus enters the squamous epithelium via a diffusion-based mechanism, but the mechanism of entry in columnar epithelium remained elusive.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, King's College London, London SE1 9RT, United Kingdom.
Oral squamous cell carcinoma (OSCC) is a subtype of head and neck cancer that arises in the multilayered epithelia of the mouth and lips. Although inactivating mutations in are frequently found in human OSCC their role in the disease is unknown. To investigate this, we deleted in the oral epithelium of adult mice.
View Article and Find Full Text PDFEMBO J
January 2025
School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3).
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