Dataset Information

The Oncogenic Kaposi's Sarcoma-Associated Herpesvirus Encodes a Mimic of the Tumor-Suppressive miR-15/16 miRNA Family.

ABSTRACT: Many tumor viruses encode oncogenes of cellular origin. Here, we report an oncoviral mimic of a cellular tumor suppressor. The Kaposi's sarcoma-associated herpesvirus (KSHV) microRNA (miRNA) miR-K6-5p shares sequence similarity to the tumor-suppressive cellular miR-15/16 miRNA family. We show that miR-K6-5p inhibits cell cycle progression, a hallmark function of miR-16. miR-K6-5p regulates conserved miR-15/16 family miRNA targets, including many cell cycle regulators. Inhibition of miR-K6-5p in KSHV-transformed B cells confers a significant growth advantage. Altogether, our data show that KSHV encodes a functional mimic of miR-15/16 family miRNAs. While it is exceedingly well established that oncogenic viruses encode oncogenes of cellular origin, this is an unusual example of an oncogenic virus that encodes a viral mimic of a cellular tumor suppressor. Encoding a tumor-suppressive miRNA could help KSHV balance viral oncogene expression and thereby avoid severe pathogenesis in the healthy host.

SUBMITTER: Morrison K

PROVIDER: S-EPMC6939447 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

The Oncogenic Kaposi's Sarcoma-Associated Herpesvirus Encodes a Mimic of the Tumor-Suppressive miR-15/16 miRNA Family.

Morrison Kylee K Manzano Mark M Chung Kevin K Schipma Matthew J MJ Bartom Elizabeth T ET Gottwein Eva E

Cell reports 20191201 10

Many tumor viruses encode oncogenes of cellular origin. Here, we report an oncoviral mimic of a cellular tumor suppressor. The Kaposi's sarcoma-associated herpesvirus (KSHV) microRNA (miRNA) miR-K6-5p shares sequence similarity to the tumor-suppressive cellular miR-15/16 miRNA family. We show that miR-K6-5p inhibits cell cycle progression, a hallmark function of miR-16. miR-K6-5p regulates conserved miR-15/16 family miRNA targets, including many cell cycle regulators. Inhibition of miR-K6-5p in ...[more]

PMID: 31801064

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Project description:MicroRNAs (miRNAs) are the non-coding RNAs that can both attach to the untranslated and coding sections of target mRNAs, triggering destruction or post-transcriptional alteration. miRNAs regulate various cellular processes such as immune function, apoptosis, and tumorigenesis. About 35,000 miRNAs have been discovered in the human genome. The increasing evidence suggests that the dysregulation of human miRNAs may have a role in the etiology of some disorders including cancer. Only a small sub-set of human miRNAs has functionally been validated in the pathogenesis of oncogenic viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the cause of various human malignancies including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS), which are mainly seen in AIDS patients or other immunocompromised people. We aimed to identify the miRNAs in Kaposi's sarcoma cases, with the comparison of KSHV seropositive and seronegative tumors with the controls and in each other in Turkish Kaposi's sarcoma patients. We performed the miRNA-sequencing at genome level in the peripheral blood mononuclear cells of 16 Kaposi's sarcoma patients, and in 8 healthy controls matched for age, gender, and ethnicity. A total of 642 miRNA molecules with different expression profiles were identified between the patients and the healthy controls. Currently, out of 642 miRNAs, 7 miRNAs (miR-92b-3p, miR-490-3p, miR-615-3p, miR-629-5p, miR-1908, miR-3180, miR-4433b-3p) which have not been described in the literature in the context of Kaposi's sarcoma were addressed in the study for the first time and 9 novel miRNAs, not found previously in the database, have been detected in Kaposi's sarcoma using the miRNA-sequencing technique. This study demonstrates the identification of differently expressed miRNAs which might be the new therapeutic targets for Kaposi's sarcoma, that has limited treatment options and can be used in the etiology, diagnosis, and prognosis of this cancer.

Dataset Information

The Oncogenic Kaposi's Sarcoma-Associated Herpesvirus Encodes a Mimic of the Tumor-Suppressive miR-15/16 miRNA Family.

Publications

The Oncogenic Kaposi's Sarcoma-Associated Herpesvirus Encodes a Mimic of the Tumor-Suppressive miR-15/16 miRNA Family.

Similar Datasets

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