LncRNA HCP5 promotes triple negative breast cancer progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p. Wang L et al. (2019) Emerging evidence has suggested that long noncoding RNAs (lncRNA) involved in the development and progression of cancer. Triple negative breast cancer (TNBC) was an aggressive type of breast cancer with high rates of cancer recurrence and metastasis. The pathogenesis of TNBC is largely unknown. Recent studies suggested that lncRNA HCP5 plays an important role in carcinogenesis. The purpose of this study was to examine the function and mechanism of HCP5 in TNBC. We observed that HCP5 was upregulated in TNBC cell lines and specimens. HCP5 knockdown induced TNBC cell apoptosis, and inhibited cell proliferation and orthotopic xenograft tumor growth. RNA sequencing and antibody array suggested that HCP5 achieves its functions through regulating apoptosis pathway. Bioinformatics, luciferase and RIP experiments proved that both HCP5 and BIRC3 could competitively bind to miR-219a-5p. Increased BIRC3 and decreased miR-219a-5p were observed in TNBC tissues and cell lines. We then performed gain- and loss-of-function studies as well as rescue experiments in TNBC cells. The decrease of proliferation and migration due to HCP5 knockdown could be rescued when miR-219a-5p inhibitor or BIRC3 was transfected and vice versa. Our study suggested that lncRNA HCP5 promotes TNBC progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p. In a word, we revealed a new signaling pathway to mediate TNBC, and provided HCP5 as a new target for improving treatment of TNBC.//////////////////
General function
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Cellular localization
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Ovarian function
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LncRNA HCP5 promotes cell proliferation and inhibits apoptosis via miR-27a-3p/IGF-1 axis in human granulosa-like tumor cell line KGN. Chen Y et al. (2019) This study aimed to reveal the potential roles of long non-coding RNA HCP5 (lncRNA HCP5) and its potential molecular mechanism in polycystic ovarian syndrome (PCOS). The human granulosa-like tumor cell line KGN was used for assessing the effects of HCP5 in the proliferation and apoptosis of granulosa cells (GCs). The results showed that downregulation of HCP5 suppressed cell proliferation through arresting cell cycle progression at G1 phase, and induced the apoptosis via activating mitochondrial pathway, while overexpression of HCP5 played the opposite effects in KGN cells. We predicted and confirmed miR-27a-3p was a directly target to HCP5 and it could directly bind with insulin-like growth factor-1 (IGF-1). Next, we performed gain- and loss-of-functions approaches by transfecting miR-27a-3p inhibitor into HCP5 knocking down cells and transfecting miR-27a-3p mimics into HCP5 overexpressing cells. The results demonstrated that downregulation and upregulation of miR-27a-3p could block the effects on the proliferation and apoptosis mediated by silencing and overexpressing HCP5 in KGN cells. Additionally, miR-27a-3p inhibitor remarkably reversed the IGF-1 decrease regulated by knocking down HCP5 and miR-27a-3p mimics inhibited the IGF-1 increase modulated by overexpressing HCP5 in KGN cells. Furthermore, we observed that the promoted cell vitality and reduced apoptosis mediated by enforced expression of HCP5 could be alleviated when the KGN cells transfected with IGF-1 siRNA. Our findings indicate that HCP5 might be a potential regulatory factor for development of PCOS through regulating the miR-27a-3p/IGF-1 axis.//////////////////
Expression regulated by
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Ovarian localization
Granulosa
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Follicle stages
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Phenotypes
POF (premature ovarian failure)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1. Wang X et al. (2020) The genetic etiology of premature ovarian insufficiency (POI) has been well established to date, however, the role of long noncoding RNAs (lncRNAs) in POI is largely unknown. In this study, we identified a down-expressed lncRNA HCP5 in granulosa cells (GCs) from biochemical POI (bPOI) patients, which impaired DNA damage repair and promoted apoptosis of GCs. Mechanistically, we discovered that HCP5 stabilized the interaction between YB1 and its partner ILF2, which could mediate YB1 transferring into the nucleus of GCs. HCP5 silencing affected the localization of YB1 into nucleus and reduced the binding of YB1 to the promoter of MSH5 gene, thereby diminishing MSH5 expression. Taken together, we identified that the decreased expression of HCP5 in bPOI contributed to dysfunctional GCs by regulating MSH5 transcription and DNA damage repair via the interaction with YB1, providing a novel epigenetic mechanism for POI pathogenesis.//////////////////