ABSTRACT
Long noncoding RNA DNAJC3-AS1 (lncRNA DNAJC3-AS1) has been probed in many studies, while the regulatory mechanism of DNAJC3-AS1 on papillary thyroid carcinoma (PTC) via regulating microRNA (miR)-27a-3p remains inadequate. This research aims to depict the role of DNAJC3-AS1, miR-27a-3p, collagen, and calcium-binding EGF domain-containing protein 1 (CCBE1) on PTC development. DNAJC3-AS1, miR-27a-3p, and CCBE1 expression levels in PTC tissues and adjacent normal tissues were tested. The relation of DNAJC3-AS1, miR-27a-3p, and CCBE1 was analyzed. DNAJC3-AS1 and miR-27a-3p and CCBE1-related oligonucleotides were transfected into IHH-4 cells to investigate their role in PTC development. Cell tumorigenicity was detected by in vivo assay. DNAJC3-AS1 and CCBE1 expressed highly and miR-27a-3p expressed lowly in PTC. Downregulation of DNAJC3-AS1, upregulating miR-27a-3p or downregulating CCBE1 impaired the malignant behaviors of IHH-4 cells. Depletion of miR-27a-3p reversed the DNAJC3-AS1 suppression-induced phenotypic inhibition of IHH-4 cells. DNAJC3-AS1 bound to miR-27a-3p and CCBE1 as a target of miR-27a-3p. Our study highlights that DNAJC3-AS1 inhibits miR-27a-3p to promote CCBE1 expression, thereby facilitating PTC development. This study affords distinguished therapeutic strategies and novel research directions for PTC treatment.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Cell Proliferation/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Cell Movement , HSP40 Heat-Shock Proteins/genetics , HSP40 Heat-Shock Proteins/metabolism , Calcium-Binding Proteins/metabolism , Tumor Suppressor Proteins/metabolismABSTRACT
Thyroid cancer (TC) is a prevailing malignant disease in endocrine system. Recent reports have demonstrated that long non-coding RNAs (lncRNAs) are crucial participators in TC progression. In our study, we majorly investigated the molecular mechanism of neuropeptide S receptor 1 antisense RNA 1 (NPSR1-AS1) in TC. Western blot and qPCR analyses were applied for the measurement of protein and RNA expressions in TC cells. Colony formation, EdU, and transwell assays, supported by western blot analyses, were implemented for probing NPSR1-AS1 impacts on TC cell malignant phenotype. Moreover, bioinformatics prediction, RIP and Actinomycin D assays detected the downstream mechanism of NPSR1-AS1 in TC cells. In short, NPSR1-AS1 displayed high expression TC cells, and NPSR1-AS1 silence inhibited TC cell malignant behaviors. Additionally, NPSR1-AS1 positively regulated its nearby gene neuropeptide S receptor 1 (NPSR1). ELAV like RNA binding protein 1 (ELAVL1) served as the RNA-binding protein (RBP) to combine with NPSR1-AS1 and NPSR1. Silencing of ELAVL1 reduced the stability of NPSR1 mRNA. Moreover, NPSR1 could activate the mitogen-activated protein kinases (MAPK) pathway in TC cells. Collectively, our study elucidated the aspect of lncRNA-RBP-mRNA interaction which might be a novel sight for TC treatment.[Figure: see text].
Subject(s)
MicroRNAs , Neuropeptides , RNA, Long Noncoding , Thyroid Neoplasms , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , ELAV-Like Protein 1/genetics , ELAV-Like Protein 1/metabolism , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Mitogen-Activated Protein Kinases/metabolism , Neuropeptides/genetics , Neuropeptides/metabolism , RNA, Antisense/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , Receptors, G-Protein-Coupled/metabolism , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathologyABSTRACT
Background: Young women with breast cancer are determined to present poorer survival compare with elderly patients. Therefore, identifying the clinical prognostic factors in young women with early-stage (T1-2N0-1M0) breast cancer is pivotal for surgeons to make better postoperative management. Methods: The clinicopathological characteristics of female patients with early-stage breast cancer from the Surveillance, Epidemiology, and End Results program between Jan 2010 and Dec 2015 were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analyses were used to determine the potential risk factors of cancer-specific survival in young women with early-stage breast cancer. The nomogram was constructed and further evaluated by an internal validation cohort. The Kaplan-Meier survival curves were used to estimate cancer-specific survival probability and the cumulative incidence. Results: Six variables including race, tumor location, grade, regional lymph node status, tumor subtype, and size were identified to be significantly associated with the prognosis of young women with early-stage breast cancer during the postoperative follow-up. A nomogram for predicting the 3-, 5- year cancer-specific survival probability in this subpopulation group was established with a favorable concordance index of 0.783, supported by an internal validation cohort with the AUC of 0.722 and 0.696 in 3-, 5- year cancer-specific survival probability, respectively. Conclusions: The first predictive nomogram containing favorable discrimination is successfully established and validated for predicting the 3-, 5- year cancer-specific survival probability in young women with early-stage breast cancer during the postoperative follow-up. This model would help clinicians to make accurate treatment decisions in different clinical risk population.
