Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity

Heindl, Andreas; Khan, Asifullah; Rodrigues, Daniel Nava; Eason, Katherine; Sadanandam, Anguraj; Orbegoso, Cecilia; Punta, Marco; Sottoriva, Andrea; Lise, Stefano; Banerjee, Susana; Yuan, Yinyin

doi:10.1038/s41467-018-06130-3

Cited by 41 publications

(29 citation statements)

References 73 publications

(80 reference statements)

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“…However, the recurrence rate is high, drug resistance is strong and the prognosis is unfavorable. Especially for patients with late, the 5-year survival rate of ovary is less than 40 percent [6]. Improving the current situation needs susceptive early detection index and new therapeutic targets [3,7].…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis

et al. 2020

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Background: Ovarian cancer (OC) is a common fatal malignant tumor of female reproductive system worldwide. Growing studies have proofed that circular RNAs (circRNAs) engage in the regulation of various types of cancers. However, the underlying biological functions and effect mechanism of circular RNA_LARP4 (circ_LARP4) in OC have not been explored. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to detect the expression of circ_LARP4 in OC cells. The function of circ_LARP4 was measured by cell counting kit-8 (CCK-8), colony formation assay and transwell assay. RNA immunoprecipitation (RIP) assay and luciferase reporter assays assessed the binding correlation between miR-513b-5p and circ_LARP4 (or LARP4). Results: The expression of circ_LARP4 in OC cells was much lower than that in human normal ovarian epithelial cells. Overexpressing circ_LARP4 impaired cell proliferation, invasion and migration abilities. Circ_LARP4 worked as a competing endogenous RNA (ceRNA) to sponge miR-513b-5p. Furthermore, LARP4 was indirectly modulated by circ_LARP4 as the downstream target of miR-513b-5p, as well as the host gene of circ_LARP4. Conclusion: Circ_LARP4 could hamper cell proliferation and migration by sponging miR-513b-5p to regulate the expression of LARP4. This research may provide some referential value to OC treatment.

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Section: Introductionmentioning

confidence: 99%

Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis

et al. 2020

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“…For every cell nucleus morphological features such as shape, intensity and texture features were calculated. Cell classification was based on a support vector (15,16) using 97 morphological and textural features. Each cell was classified into artefact, lymphocyte, cancer, or stromal cell.…”

Section: Hande Image Processingmentioning

confidence: 99%

Topological Tumor Graphs: A Graph-Based Spatial Model to Infer Stromal Recruitment for Immunosuppression in Melanoma Histology

et al. 2020

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Despite the advent of immunotherapy, metastatic melanoma represents an aggressive tumor type with a poor survival outcome. The successful application of immunotherapy requires in-depth understanding of the biological basis and immunosuppressive mechanisms within the tumor microenvironment. In this study, we conducted spatially explicit analyses of the stromal-immune interface across 400 melanoma hematoxylin and eosin (H&E) specimens from The Cancer Genome Atlas. A computational pathology pipeline (CRImage) was used to classify cells in the H&E specimen into stromal, immune, or cancer cells. The estimated proportions of these cell types were validated by independent measures of tumor purity, pathologists' estimate of lymphocyte density, imputed immune cell subtypes, and pathway analyses. Spatial interactions between these cell types were computed using a graphbased algorithm (topological tumor graphs, TTG). This approach identified two stromal features, namely stromal clustering and stromal barrier, which represented the melano-ma stromal microenvironment. Tumors with increased stromal clustering and barrier were associated with reduced intratumoral lymphocyte distribution and poor overall survival independent of existing prognostic factors. To explore the genomic basis of these TTG-derived stromal phenotypes, we used a deep learning approach integrating genomic (copy number) and transcriptomic data, thereby inferring a compressed representation of copy number-driven alterations in gene expression. This integrative analysis revealed that tumors with high stromal clustering and barrier had reduced expression of pathways involved in na€ ve CD4 signaling, MAPK, and PI3K signaling. Taken together, our findings support the immunosuppressive role of stromal cells and T-cell exclusion within the vicinity of melanoma cells. Significance: Computational histology-based stromal phenotypes within the tumor microenvironment are significantly associated with prognosis and immune exclusion in melanoma.

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“…5 The five-year survival rate of OC patients remains lower than 35%. 6 Thus, determining the factors regulating OC development and identifying effective therapeutic targets are urgently required.…”

Section: Introductionmentioning

confidence: 99%

<p>lncRNA RHPN1-AS1 Promotes Ovarian Cancer Growth and Invasiveness Through Inhibiting miR-1299</p>

Zhao¹,

Liu²,

Zhang³

et al. 2020

OTT

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Background: Ovarian cancer (OC) is a big threat for public health. However, the molecular mechanism underlying OC development and progression remains unclear. Although the importance of lncRNA in cancer has been proven, how lncRNA is involved in OC is waiting for further investigation. Materials and Methods: qRT-PCR was performed to test expression level. CCK8 and colony formation were conducted to analyze proliferation. Transwell was conducted to measure migration and invasion. Luciferase reporter assay and pulldown assay were utilized to validate RNA interaction. Results: lncRNA RHPN1-AS1 was highly expressed in OC tissues. RHPN1-AS1 was positively correlated with OC progression and its high expression indicated a low survival rate. Moreover, knockdown of RHPN1-AS1 significantly inhibited the proliferation, migration and invasion of OC cells, and bioinformatics analysis identified that miR-1299 was sponged by RHPN1-AS1 in OC cells. Knockdown of RHPN1-AS1 markedly promoted miR-1299 expression. Of note, inhibition of miR-1299 reversed the roles of RHPN1-AS1 silencing on suppressing proliferation, migration and invasion. Conclusion: Our study demonstrates that RHPN1-AS1 promotes OC progression via sponging miR-1299, suggesting RHPN1-AS1 may be a novel therapeutic target.

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Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity

Cited by 41 publications

References 73 publications

Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis

Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis

Topological Tumor Graphs: A Graph-Based Spatial Model to Infer Stromal Recruitment for Immunosuppression in Melanoma Histology

<p>lncRNA RHPN1-AS1 Promotes Ovarian Cancer Growth and Invasiveness Through Inhibiting miR-1299</p>

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