Novel lncRNA LINC00844 Regulates Prostate Cancer Cell Migration and Invasion through AR Signaling

Abstract

: The human genome is mostly transcribed, yielding a rich repository of noncoding transcripts that are involved in a myriad of biological processes including cancer. However, how many noncoding transcripts such as long noncoding RNAs (lncRNA) function in cancer is still unclear. This study identified a novel set of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this group, was demonstrated to be a direct androgen-regulated target that is actively transcribed in androgen receptor (AR)-dependent prostate cancer cells. The expression of is higher in normal prostate compared with malignant and metastatic prostate cancer clinical specimens, and patients with low expression had a poor prognosis and significantly increased biochemical recurrence, suggesting functions in suppressing tumor progression and metastasis. Indeed, loss-of-function studies revealed that prevents prostate cancer cell migration and invasion. Moreover, findings from gene expression profiling analysis indicated that functions in , affecting global androgen-regulated gene transcription. Mechanistic evidence reveals that is important in facilitating AR binding to the chromatin. Finally, mediates its phenotypic effects in part by activating the expression of, a crucial cancer metastasis suppressor. Collectively, is a novel coregulator of AR that plays a central role in the androgen transcriptional network and the development and progression of prostate cancer. IMPLICATIONS: This study highlights the function of the lncRNA,, in regulating global AR-regulated genes in prostate cancer by modulating AR binding to chromatin.

lncRNA HCG11 regulates cell progression by targeting miR‐543 and regulating AKT/mTOR pathway in prostate cancer

“…Previous studies have reported that non‐coding RNAs (ncRNAs) play important roles in cancer development, tumor formation, immune response, and inflammation of many cancers, which includes small ncRNAs (<200 nucleotides at length) and long ncRNAs (lncRNA, >200 nucleotides at length) (Bushati and Cohen, ; Krol et al, ; Perkel, ; Rapicavoli et al, ; Tao et al, ). Emerging evidence suggested that lncRNA is involved in cell proliferation, invasion, migration, and apoptosis in multiple types of cancers, including PCa (Guo et al, ; Li et al, ; Zhang et al, ; Lingadahalli et al, ). Chakravarty et al () reported that lncRNA NEAT1 was a critical modulator in cell progression of PCa.…”

Peer Review #1 of "LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression (v0.2)"

“…Genome-wide sequencing has revealed the involvement of more and more lncRNAs in different types of cancers [10] . Lingadahalli et al [19] performed in vivo and in vitro experiments to confirm the participation of LINC00844 in tumour metastasis partly through its effect on the expression of NDRG1 in prostate cancer. High expression of lncPARP1 may serve as an adverse prognosis factor for HCC [20] .…”

“…A study reported that NDRG1 overexpression may inhibit the expression of E-cadherin and enhance the expression of Snail, and consequently regulate tumour growth and metastasis in oesophageal squamous cell carcinoma [18] . Another study reported that LINC00844 exerted its antitumour activity by regulating the expression of NDRG1 in prostate cancer [19] . However, the biological function and underlying molecular mechanisms of LINC00844 in HCC are unclear.…”

Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF‐1α/Notch‐1 signaling pathway via KLF2

“…LncRNAs could regulate PC development through different signaling pathways . Previous studies have indicated the association between PC and Notch‐1 signaling pathway .…”