Down Regulation of miR-34a and miR-143 May Indirectly Inhibit p53 in Oral Squamous Cell Carcinoma: a Pilot Study.

Mayakannan Manikandan,Kottayasamy Seenivasagam Rajkumar,Ramamurthy Rajaraman,Arunagiri Kuha Deva Magendhra Rao,Arasambattu Kannan Munirajan,Ganesan Arunkumar

doi:10.7314/apjcp.2015.16.17.7619

Mayakannan Manikandan, Kottayasamy Seenivasagam Rajkumar + Show 4 more

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https://doi.org/10.7314/apjcp.2015.16.17.7619

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Aberrant microRNA expression has been associated with the pathogenesis of a variety of human malignancies including oral squamous cell carcinoma (SCC). In this study, we examined primary oral SCCs for the expression of 6 candidate miRNAs, of which five (miR-34a, miR-143, miR-373, miR-380-5p, and miR- 504) regulate the tumor suppressor TP53 and one (miR-99a) is involved in AKT/mTOR signaling. Tumor tissues (punch biopsies) were collected from 52 oral cancer patients and as a control, 8 independent adjacent normal tissue samples were also obtained. After RNA isolation, we assessed the mature miRNA levels of the 6 selected candidates against RNU44 and RNU48 as endogenous controls, using specific TaqMan miRNA assays. miR-34a, miR-99a, miR-143 and miR-380-5p were significantly down-regulated in tumors compared to controls. Moreover, high levels of miR-34a were associated with alcohol consumption while those of miR-99a and miR-143 were associated with advanced tumor size. No significant difference was observed in the levels of miR-504 between the tumors and controls whereas miR-373 was below the detection level in all but two tumor samples. Low levels of miR-380-5p and miR-504 that directly target the 3'UTR of TP53 suggest that p53 may not be repressed by these two miRNAs in OSCC. On the other hand, low levels of miR-34a or miR-143 may relieve MDM4 and SIRT1 or MDM2 respectively, which will sequester p53 indicating an indirect mode of p53 suppression in oral tumors.

Highlights

Oral squamous cell carcinoma (OSCC) is one of the major public health problems and is the sixth common human malignancy worldwide (Parkin et al, 2005)
Aberrant microRNA expression has been associated with the pathogenesis of a variety of human malignancies including oral squamous cell carcinoma (SCC)
We examined primary oral SCCs for the expression of 6 candidate miRNAs, of which five regulate the tumor suppressor TP53 and one is involved in AKT/mTOR signaling

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is one of the major public health problems and is the sixth common human malignancy worldwide (Parkin et al, 2005). Aberrant microRNA expression has been associated with the pathogenesis of a variety of human malignancies including oral squamous cell carcinoma (SCC). We examined primary oral SCCs for the expression of 6 candidate miRNAs, of which five (miR-34a, miR-143, miR-373, miR-380-5p, and miR504) regulate the tumor suppressor TP53 and one (miR-99a) is involved in AKT/mTOR signaling. Conclusions: Low levels of miR-380-5p and miR-504 that directly target the 3’UTR of TP53 suggest that p53 may not be repressed by these two miRNAs in OSCC. Low levels of miR-34a or miR-143 may relieve MDM4 and SIRT1 or MDM2 respectively, which will sequester p53 indicating an indirect mode of p53 suppression in oral tumors

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