2017The FASEB JournalRequires access

Investigation of PAX3‐FOXO1 Effect on NEAT1 Expression in Alveolar Rhabdomyosarcoma Cells

Victoria Agbeke George, Brianyell McDaniel, Kelly Johanson

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Abstract

Rhabdomyosarcoma (RMS) is pediatric sarcoma in the soft muscular tissue. One of the two major types of rhabdomyosarcoma is alveolar rhabdomyosarcoma (ARMS). ARMS generally occurs in muscles in the abdomen, arms, and legs. Due to its tendency to grow more rapidly, it is a more aggressive form of the cancer that has a higher risk factor than other forms of RMS. The expression of PAX3‐FOXO1 in ARMS may contribute to the formation of tumors by inducing tumor growth activities or inhibiting tumor suppressing activities. There are many studies investigating targets of PAX3‐FOXO1 and some indicate that PAX3‐FOXO1 binds to long noncoding RNA (lncRNA), although it is not known if this interaction affects the expression of the lncRNA. Nuclear‐enriched autosomal transcript 1 (NEAT1) is a 4kb lncRNA that potentially is bound by PAX3‐FOXO1. Several putative PAX3‐FOXO1 binding sites are present in the DNA fragment of NEAT1 that was identified in a ChIP assay. We are examining the NEAT1 sequence to narrow down the specific site of PAX3‐FOXO1 interaction as well as determining the effect of PAX3‐FOXO1 on NEAT1 expression. The expression of NEAT1 is necessary for differentiation of muscle cells and a change in this expression due to PAX3‐FOXO1 may be linked to ARMS development. Finding the effect of PAX3‐FOXO1 on expression of NEAT1 will help to uncover more information about the mechanisms involved in the development and progression of ARMS. Support or Funding Information NIH BUILD TL4GM118968, NIH BUILD RL5GM118966‐02

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What this paper is about

Rhabdomyosarcoma (RMS) is pediatric sarcoma in the soft muscular tissue. One of the two major types of rhabdomyosarcoma is alveolar rhabdomyosarcoma (ARMS). ARMS generally occurs in muscles in the abdomen, arms, and legs. Due to its tendency to grow more rapidly, it is a more aggressive form of the cancer that has a higher risk factor than other forms of RMS. The expression of PAX3‐FOXO1 in ARMS may contribute to the formation of tumors by inducing tumor growth activities or inhibiting tumor suppressing activities. There are many studies investigating targets of PAX3‐FOXO1 and some indicate that PAX3‐FOXO1 binds to long noncoding RNA (lncRNA), although it is not known if this interaction affects the expression of the lncRNA. Nuclear‐enriched autosomal transcript 1 (NEAT1) is a 4kb lncRNA that potentially is bound by PAX3‐FOXO1. Several putative PAX3‐FOXO1 binding sites are present in the DNA fragment of NEAT1 that was identified in a ChIP assay. We are examining the NEAT1 sequence to narrow down the specific site of PAX3‐FOXO1 interaction as well as determining the effect of PAX3‐FOXO1 on NEAT1 expression. The expression of NEAT1 is necessary for differentiation of muscle cells and a change in this expression due to PAX3‐FOXO1 may be linked to ARMS development. Finding the effect of PAX3‐FOXO1 on expression of NEAT1 will help to uncover more information about the mechanisms involved in the development and progression of ARMS. Support or Funding Information NIH BUILD TL4GM118968, NIH BUILD RL5GM118966‐02

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Available abstract

Rhabdomyosarcoma (RMS) is pediatric sarcoma in the soft muscular tissue. One of the two major types of rhabdomyosarcoma is alveolar rhabdomyosarcoma (ARMS). ARMS generally occurs in muscles in the abdomen, arms, and legs. Due to its tendency to grow more rapidly, it is a more aggressive form of the cancer that has a higher risk factor than other forms of RMS. The expression of PAX3‐FOXO1 in ARMS may contribute to the formation of tumors by inducing tumor growth activities or inhibiting tumor suppressing activities. There are many studies investigating targets of PAX3‐FOXO1 and some indicate that PAX3‐FOXO1 binds to long noncoding RNA (lncRNA), although it is not known if this interaction affects the expression of the lncRNA. Nuclear‐enriched autosomal transcript 1 (NEAT1) is a 4kb lncRNA that potentially is bound by PAX3‐FOXO1. Several putative PAX3‐FOXO1 binding sites are present in the DNA fragment of NEAT1 that was identified in a ChIP assay. We are examining the NEAT1 sequence to narrow down the specific site of PAX3‐FOXO1 interaction as well as determining the effect of PAX3‐FOXO1 on NEAT1 expression. The expression of NEAT1 is necessary for differentiation of muscle cells and a change in this expression due to PAX3‐FOXO1 may be linked to ARMS development. Finding the effect of PAX3‐FOXO1 on expression of NEAT1 will help to uncover more information about the mechanisms involved in the development and progression of ARMS. Support or Funding Information NIH BUILD TL4GM118968, NIH BUILD RL5GM118966‐02

Key concepts: Alveolar rhabdomyosarcoma, PAX3, FOXO1, Rhabdomyosarcoma, Cancer research, Biology, Cancer, Gene

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Investigation of PAX3‐FOXO1 Effect on NEAT1 Expression in Alveolar Rhabdomyosarcoma Cells — Research Paper | ScholarLens