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Bone metastasis is an incurable complication of breast cancer. In advanced stages, patients with estrogen-positive tumors experience a significantly higher incidence of bone metastasis (>87%) compared to estrogen-negative patients (, Bone metastasis is a major complication of breast cancer (BC) and ER+ tumors have a higher incidence of bone metastasis than ER− tumors. Here, the authors report that miR‐19a in exosomes and the bone matrix protein, IBSP, are upregulated and secreted by bone tropic ER+ BC cells, where they cooperatively induce osteoclastogenesis and promote bone colonization.

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., The function of many human long non-coding RNAs (lncRNAs) is still undetermined. Here, the authors setup a gain of function CRISPR-based screen and identify a lncRNA that positively regulates AKT activity by interacting with the RNA helicase DHX9 resulting in stabilization of PI3K regulatory subunit p85.