The interplay between viruses &amp; host microRNAs in cancer – An emerging role for HIV in oncogenesis

Mapekula, Lungile; Ramorola, Beatrice Relebogile; Hoosen, Taahira Goolam; Mowla, Shaheen

doi:10.1016/j.critrevonc.2019.02.007

Cited by 3 publications

(3 citation statements)

References 81 publications

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“…This concern can be reduced by modifications removing replication and integration activities but this also removes a major lentiviral benefit. 66–68 Lentivirus-transduced cells are tested for these issues prior to transplant but such testing is not amenable for a direct treatment approach in which the virus is administered directly to the patient. Future modifications to lentivirus may reduce or eliminate these concerns.…”

Section: Viral Vectorsmentioning

confidence: 99%

Pulmonary gene delivery—Realities and possibilities

Baliga

Dean

2020

Exp Biol Med (Maywood)

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Delivery of genetic material to tissues in vivo is an important technique used in research settings and is the foundation upon which clinical gene therapy is built. The lung is a prime target for gene delivery due to a host of genetic, acquired, and infectious diseases that manifest themselves there, resulting in many pathologies. However, the in vivo delivery of genetic material to the lung remains a practical problem clinically and is considered the major obstacle needed to be overcome for gene therapy. Currently there are four main strategies for in vivo gene delivery to the lung: viral vectors, liposomes, nanoparticles, and electroporation. Viral delivery uses several different genetically modified viruses that enter the cell and express desired genes that have been inserted to the viral genome. Liposomes use combinations of charged and neutral lipids that can encapsulate genetic cargo and enter cells through endogenous mechanisms, thereby delivering their cargoes. Nanoparticles are defined by their size (typically less than 100 nm) and are made up of many different classes of building blocks, including biological and synthetic polymers, cell penetrant and other peptides, and dendrimers, that also enter cells through endogenous mechanisms. Electroporation uses mild to moderate electrical pulses to create pores in the cell membrane through which delivered genetic material can enter a cell. An emerging fifth category, exosomes and extracellular vesicles, may have advantages of both viral and non-viral approaches. These extracellular vesicles bud from cellular membranes containing receptors and ligands that may aid cell targeting and which can be loaded with genetic material for efficient transfer. Each of these vectors can be used for different gene delivery applications based on mechanisms of action, side-effects, and other factors, and their use in the lung and possible clinical considerations is the primary focus of this review.

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Section: Viral Vectorsmentioning

confidence: 99%

Pulmonary gene delivery—Realities and possibilities

Baliga

Dean

2020

Exp Biol Med (Maywood)

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“…This is likely to include alterations in miRNA expression. Oncogenic viruses such as the Epstein–Barr virus (EBV) and the Kaposi’s sarcoma-associated herpesvirus (KSHV), both of which are closely associated with HIV infection and the development of lymphoproliferative diseases, have been shown to alter the expression of a wide array of cellular miRNAs, with roles linked to the oncogenic process [ 19 ]. Although several studies have described specific miRNA expression signatures for various cancers including BL, none have described how these signatures may differ in the presence of HIV.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Cellular MicroRNA by HIV-1 in Burkitt Lymphoma Cells—A Pathway to Promoting Oncogenesis

Ramorola

Goolam-Hoosen

Rios

et al. 2021

Genes

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Viruses and viral components have been shown to manipulate the expression of host microRNAs (miRNAs) to their advantage, and in some cases to play essential roles in cancer pathogenesis. Burkitt lymphoma (BL), a highly aggressive B-cell derived cancer, is significantly over-represented among people infected with HIV. This study adds to accumulating evidence demonstrating that the virus plays a direct role in promoting oncogenesis. A custom miRNA PCR was used to identify 32 miRNAs that were differently expressed in Burkitt lymphoma cells exposed to HIV-1, with a majority of these being associated with oncogenic processes. Of those, hsa-miR-200c-3p, a miRNA that plays a crucial role in cancer cell migration, was found to be significantly downregulated in both the array and in single-tube validation assays. Using an in vitro transwell system we found that this downregulation correlated with significantly enhanced migration of BL cells exposed to HIV-1. Furthermore, the expression of the ZEB1 and ZEB2 transcription factors, which are promotors of tumour invasion and metastasis, and which are direct targets of hsa-miR-200c-3p, were found to be enhanced in these cells. This study therefore identifies novel miRNAs as role players in the development of HIV-associated BL, with one of these miRNAs, hsa-miR-200c-3p, being a candidate for further clinical studies as a potential biomarker for prognosis in patients with Burkitt lymphoma, who are HIV positive.

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“…CircRNAs were grouped into four categorized [ 7 ] due to there structure. Moreover, circRNAs [ 8 ] were discovered in various eukaryotic organisms from protists to humans and accumulating evidence [ 9 ] showed that circRNAs were abnormally expressed in multiple types of malignant tumors and these dysregulated circRNAs contributed to the diagnosis and prognosis of patients, such as thyroid cancer, epithelial ovarian cancer, hepatocellular carcinoma, cervical cancer and colorectal cancer [ 10 – 14 ]. Substantial evidence [ 15 , 16 ] has revealed that circRNAs play vital roles in regulating potential biological functions of cancers by acting as miRNA sponge ; regulating gene splicing, transcription and translation; serving on autophagy regulator and interacting with RNA-Binding proteins (RBPs).…”

Section: Introductionmentioning

confidence: 99%

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

Pan

Zhang²,

Tang³

et al. 2020

Cancer Cell Int

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Background Recently, it has been demonstrated that circular RNA (circRNA) contributes to the production and progression in human cancer. However, the specific function and underlying mechanism of circ_0028171 in osteosarcoma (OS) still remain largely unclear and require to be investigated. Methods In our study, we confirmed differentially expressed circRNAs by microarray analysis in normal bone cells vs. OS cell lines. The expression of circ-0028171 in OS was measured by qRT-PCR. Nuclear-cytoplasmic fractionation was employed to identify the localization of circ-0028171, and RNase R and actinomycin D treatment were used to prove its circular characteristic. In vitro experiments, such as CCK-8 method, cell count, cell colony formation, transwell migration and invasion assays, and in vivo tumor models were adopted to evaluate the effect of circ_0028171. Further, luciferase reporter, RIP and RNA pull-down assays were conducted to confirm the binding sites of circ_0028171 with miR-218-5p. Results We found that circ_0028171 displayed a remarkably higher expression in both OS tissues and cell lines. Circ_0028171 mainly located in the cytoplasm as a stable cyclic transcript. Knockdown of circ_0028171 suppressed OS tumor growth in vitro and in vivo, while up-regulated circ_0028171 remarkably enhanced cell proliferation, migration and invasion abilities in OS. Several mechanistic experiments revealed that circ_0028171 served as a sponge of miR-218-5p to increase IKBKB expression. Conclusions our research reveals that circ_0028171 might promote the malignant behavior of OS tissues through miR-218-5p/IKBKB axis, which could be a potential novel marker for early diagnosis of OS.

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The interplay between viruses & host microRNAs in cancer – An emerging role for HIV in oncogenesis

Cited by 3 publications

References 81 publications

Pulmonary gene delivery—Realities and possibilities

Pulmonary gene delivery—Realities and possibilities

Modulation of Cellular MicroRNA by HIV-1 in Burkitt Lymphoma Cells—A Pathway to Promoting Oncogenesis

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

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