| Project/Area Number |
20K18289
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
小杉 隆誠 琉球大学, 医学部, 非常勤講師 (10867047)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Granted (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Head and neck cancer / Human Papillomavirus / ncRNA / HPV / squamous cell carcinoma / immune system / head and neck cancer |
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| Outline of Research at the Start |
One of the ultimate goals of modern medicine is to absolutely control virus behaviors in human diseases. The proposed research, in this unprecedented era of the worldwide pandemic, is hopefully dedicated to a progress toward the forthcoming establishment of medicine.
Human papillomavirus (HPV) is a significant infectious agent of head and neck cancer (HNC) and the mechanism of the onset of HPV-related HNC is complex in part due to tangled host-virus immunological interactions. Recently, we found novel HPV-derived non-coding RNAs that may substantiate key mechanisms for oncogenesis
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| Outline of Annual Research Achievements |
Human papillomavirus (HPV) is one of the major oncoviruses and can cause several types of cancer including head and neck cancer (HNC) and cervical cancer. Although HPV is the causing agent of cervical cancer in almost all cases, HNC comprises both HPV-related and HPV-unrelated conditions. These different pathological statuses further reflect distinct prognoses and thus understanding detailed molecular mechanisms of the etiologically distinct carcinogenesis is vital for the development of HNC clinical therapies.
Recently we found putative ncRNAs derived from HPV and the proposed study thus aims to identify their structures and functions in HPV-driven carcinogenesis. Expression analyses revealed several different sequences of HPV-derived ncRNAs expressed in squamous cell carcinoma (SCC) cell lines and tissues from HPV-positive HNC patients. Expression patterns of HPV ncRNAs seemed to be correlated with phenotypes of SCC. Subcellular fractionation and quantitative RT-PCR demonstrated the ncRNAs were localized not only in the nucleus but also in the cytoplasm. In order to functionally characterize the ncRNA expression in SCC, cells were cultured in different conditions, which are linked to potential mechanisms for carcinogenesis. On-going cell-based functional assays are uncovering changes in the quantities and the subcellular distribution in response to the different cellular conditions and will delineate molecular environments in which the ncRNAs are significantly participated.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The proposed study aims to establish three primary goals, which are (1) structural identification of the viral ncRNAs, (2) functional characterization of the viral ncRNA expression, and (3) determination of functional roles of the viral ncRNAs in cancers (SCC). We first focused on the goals (1) and (2) to clarify the functionally significant sequences expressed in SCC. Several different sequences of HPV-derived ncRNAs have been cloned and their significant involvement in potential carcinogenesis-related phenotypes has been assessed. On-going experiments are elucidating functional links between the ncRNA expression and certain cellular responses along with cancer-related molecules.
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| Strategy for Future Research Activity |
We are getting some intriguing results from on-going experiments and significant insights into further functional studies. Based on these results, we will perform some loss and gain of function experiments for the goal (3).
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