LncRNA AK023948 is a positive regulator of AKT.
Despite the overwhelming number of human long non-coding RNAs (lncRNAs) reported so far, little is known about their physiological functions for the majority of them. The present study uses a CRISPR/Cas9-based synergistic activation mediator (SAM) system to identify potential lncRNAs capable of regulating AKT activity. Among lncRNAs identified from this screen, we demonstrate that AK023948 is a positive regulator for AKT. Knockout of AK023948 suppresses, whereas rescue with AK023948 restores the AKT activity. Mechanistically, AK023948 functionally interacts with DHX9 and p85. Importantly, AK023948 is required for the interaction between DHX9 and p85 to hence the p85 stability and promote AKT activity. Finally, AK023948 is upregulated in breast cancer; interrogation of TCGA data set indicates that upregulation of DHX9 in breast cancer is associated with poor survival. Together, this study demonstrates two previously uncharacterized factors AK023948 and DHX9 as important players in the AKT pathway, and that their upregulation may contribute to breast tumour progression.
Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.|Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Pratirodh
P
Koirala
Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.|Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Jianguo
J
Huang
Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.|Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.|Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Tsui-Ting
TT
Ho
System Biosciences, Mountain View, California 94041, USA.
Fangting
F
Wu
Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.|College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310022, China.
Xianfeng
X
Ding
Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.|Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Yin-Yuan
YY
Mo
D000818:Animals; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D064113:CRISPR-Cas Systems; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases