Deletion of SMURF 1 represses ovarian cancer invasion and EMT by modulating the DAB2IP/AKT/Skp2 feedback loop

SMAD ubiquitination regulatory factor 1 (SMURF1) has been described as a tumor suppressor in multiple aggressive cancers. Nevertheless, the potential role of SMURF1 in ovarian cancer invasion and epithelial-to-mesenchymal transition (EMT) remains unclear. The aim of this study was to evaluate the efficacy of SMURF1 on tumor migration and EMT and elucidate the underlying molecular mechanism in ovarian carcinoma. We found elevated SMURF1 in several ovarian cancer cells in both messenger RNA and protein. Additionally, silencing SMURF1 apparently repressed cell proliferation and invasion capacity of SKOV3 and A2780 cells and markedly attenuated expression of linked proteins such as proliferating cellnuclear antigen, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, depletion of SMURF1 dramatically impeded EMT progress by modulating EMT biomarkers, with a notable increase in E-cadherin expression accompanied by the decrease in N-cadherin and vimentin in both SKOV3 and A2780 cells. Interestingly, elimination of SMURF1 led to disabled homolog 2 DOC-2/DAB2 interacting protein (DAB2IP) activation and dampened AKT/Skp2 signaling. Most important, depleted of DAB2IP or treatment with the AKT agonist 740Y-P effectively abolished the suppressive effects of SMURF1 knockout on cell invasiveness and EMT process. Taken all data together, these findings demonstrated that the absence of SMURF1 repressed cell proliferation, invasive capability, and EMT process in ovarian cancer through DAB2IP/AKT/Skp2 signaling loops, suggesting that SMURF1 may serve as a new potential therapeutic agent for ovarian cancer.     

LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR-335-5p

Emerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR-335-5p, isolating miR-335-5p from its target gene Rho-associated coiled-coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR-335-5p. Further cellular behavioral experiments revealed that miR-335-5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR-335-5p, suggesting a novel potential therapeutic target for cervical cancer.     

Circular RNA hsa_circ_0053277 promotes the development of colorectal cancer by upregulating matrix metallopeptidase 14 via miR-2467-3p sequestration

Colorectal cancer (CRC), a kind of human gastrointestinal cancer, has been reported to be one of the most common malignant tumors worldwide. Increasing evidence has indicated that circular RNAs exert significant effects on the development of multiple cancers. Nevertheless, whether hsa_circ_0053277 regulates the progression of CRC remains to be explored. In this study, our results showed that the expression of hsa_circ_0053277 was markedly upregulated in CRC tissues and cells. Knockdown of hsa_circ_0053277 inhibited cell proliferation, migration, and epithelial-mesenchymal transition (EMT) process in CRC. miR-2467-3p had a binding site for hsa_circ_0053277. Molecular mechanism assays confirmed that hsa_circ_0053277 could bind with miR-2467-3p. In addition, hsa_circ_0053277 accelerated cell proliferation rate by acting as a sponge for miR-2467-3p in CRC. Matrix metalloproteinase 14 (MMP14) expression was notably upregulated in CRC cells and MMP14 was a downstream target gene of miR-2467-3p. Besides, hsa_circ_0053277 positively regulated MMP14 expression while miR-2467-3p negatively regulated MMP14 expression. Rescue assays verified that MMP14 knockdown countervailed the function of miR-2467-3p inhibitor on cell proliferation, migration, and EMT process in CRC. To sum up, hsa_circ_0053277 facilitated the development of CRC by sponging miR-2467-3p to upregulate MMP14 expression.     

IncRNA MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cell lines by targeting miR-519e-5p/YWHAH

Thyroid cancer is a common malignant tumour of the endocrine system and ranks ninth in cancer incidence worldwide. An extensive body of evidence has demonstrated that lncRNAs play a critical role in the progression of thyroid cancer. The lncRNA MAPKAPK5-AS1 has been reported to be abnormally expressed and to play a role in the development of various human cancers. However, MAPKAPK5-AS1’s potential role in thyroid cancer progression remains unknown. The objective of our study was to explore the role and mechanism of MAPKAPK5-AS1 in thyroid cancer cells and provide a potential target for its biological diagnosis and treatment. We transfected sh-MAPKAPK5-AS1 and sh-NC into BCPAP and TPC-1 cells for loss-of-function assays. Results of RT-qPCR analysis demonstrated that MAPKAPK5-AS1 was more highly expressed in thyroid cancer cells compared to normal cells. Functional assays demonstrated that interfering with the expression of MAPKAPK5-AS1 notably repressed proliferation and invasion and accelerated apoptosis of BCPAP and TPC-1 cells. Mechanistically, we found that miR-519e-5p was negatively regulated by MAPKAPK5-AS1 and that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) was a target of miR-519e-5p. Additionally, rescue assays demonstrated that downregulation of MAPKAPK5-AS1 expression inhibited cell proliferation, migration, and invasion and promoted apoptosis by sponging miR-519e-5p, thereby increasing YWHAH expression. Ultimately, our study revealed that MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cells by targeting the miR-519e-5p/YWHAH axis, which provides novel insight into the development and progression of thyroid cancer.Key words: IncRNA MAPKAPK5-AS1, MiR-519e-5p, YWHAH, thyroid cancer cell     

MicroRNA-221 Mediates the Effects of PDGF-BB on Migration,Proliferation, and the Epithelial-Mesenchymal Transition in Pancreatic Cancer Cells

The platelet-derived growth factor (PDGF) signaling pathway has been found to play important roles in the development and progression of human cancers by regulating the processes of cell proliferation, apoptosis, migration, invasion, metastasis, and the acquisition of the epithelial-mesenchymal transition (EMT) phenotype. Moreover, PDGF signaling has also been found to alter the expression profile of miRNAs, leading to the reversal of EMT phenotype. Although the role of miRNAs in cancer has been documented, there are very few studies documenting the cellular consequences of targeted re-expression of specific miRNAs. Therefore, we investigated whether the treatment of human pancreatic cancer cells with PDGF could alter the expression profile of miRNAs, and we also assessed the cellular consequences. Our study demonstrates that miR-221 is essential for the PDGF-mediated EMT phenotype, migration, and growth of pancreatic cancer cells. Down-regulation of TRPS1 by miR-221 is critical for PDGF-mediated acquisition of the EMT phenotype. Additionally, the PDGF-dependent increase in cell proliferation appears to be mediated by inhibition of a specific target of miR-221 and down-regulation of p27Kip1.     

MiR-192-5p inhibits proliferation,migration, and invasion in papillary thyroid carcinoma cells by regulation of SH3RF3

Background: The decreased level of miR-192-5p has been reported in several kinds of cancers, including bladder, colon, ovarian, and non-small cell lung cancer. However, the expression and function of miR-192-5p in papillary thyroid carcinoma/cancer (PTC) remains unknown.Objective: The present study aimed to explore the function and underlying mechanism of miR-192-5p in PTC development.Methods: PTC tissues and relative normal controls from PTC patients were collected. qRT-PCR analysis was performed to measure miR-192-5p and SH3RF3 mRNA level in PTC tissues and cell lines. CCK-8 method and FCM assay were used to test cell proliferation and apoptosis in TPC-1 cells, respectively. The abilities of cell migration and invasion were detected by wound healing and transwell assays, respectively. The protein expression was evaluated by Western blot. The interaction between miR-192-5p and Src homology 3 (SH3) domain containing ring finger 3 (SH3RF3) were confirmed by dual-luciferase reporter assay.Results: MiR-192-5p level was obviously decreased in PTC tissues and cell lines. Overexpression of miR-192-5p suppressed proliferation, migration, invasion, and EMT process, while induced apoptosis in TPC-1 cells. In addition, miR-192-5p negatively modulated SH3RF3 expression by binding to its 3′-untranslated region (3′UTR). Silencing SH3RF3 inhibited the migration, invasion, and EMT of TPC-1 cells. In the meantime, matrine, an alkaloid extracted from herb, exerted its anti-cancer effects in PTC cells dependent on increase in miR-192-5p expression and decrease in SH3RF3 expression.Conclusion: We firstly declared that miR-192-5p played a tumor suppressive role in PTC via targeting SH3RF3. Moreover, matrine exerted its anti-cancer effects in PTC via regulating miR-192-5p/SH3RF3 pathway.     

Uridine phosphorylase 1 associates to biological and clinical significance in thyroid carcinoma cell lines

Thyroid cancer incidence has been continuity increasing worldwide. Uridine phosphorylase 1 (UPP1) is a protein‐coding gene and has been detected that UPP1 was the higher expression in many solid malignancies, just as head and neck cancers, breast cancer, compared with paired normal tissue. But the act of UPP1 in thyroid cancer is not explicit. In this article, we investigate the function of UPP1 expression in thyroid cancer. The Cancer Genome Atlas (TCGA) unpaired thyroid cancer and normal RNA‐seq data were downloaded, and our paired thyroid cancer and normal samples were analysed by a polymerase chain reaction. The expression of UPP1 was regulated by transfected small interfering RNA, and the function of UPP1 was determined via migration, invasion and cell proliferation assays. Western blot assay was achieved to determine the UPP1 expression correlates with the function of 5‐FU regulate epithelial‐mesenchymal transition. The significant upregulation of UPP1 in thyroid cancer tissues compared with normal thyroid tissues was revealed by our data and TCGA data. UPP1 overexpression was significantly correlated with lymph node metastasis, tumour stage and tumour size. In the cell, experiments showed that UPP1 low expression significantly suppressed the migration, invasion and proliferation. Western blot assay proves the effect of UPP1 expression on 5‐FU regulates epithelial‐mesenchymal transition pathway. UPP1 plays a crucial oncogene in thyroid cancer. Our findings indicate that UPP1 might be a biomarker of thyroid cancer and may act by regulating epithelial‐mesenchymal transition (EMT).     

Circular RNA hsa_circ_0030018 acts as a sponge of miR-599 to aggravate esophageal carcinoma progression by regulating ENAH expression

Esophageal carcinoma (EC) bears one of the most rapid-growing incidences in cancers, which also has the highest mortality rate worldwide. Multiple studies have authenticated that circular RNAs (circRNAs) significantly work on the progression of cancers. circRNA hsa_circ_0030018 was also verified to exert functions on the development of glioma previously. Nevertheless, the biological function of hsa_circ_0030018 in EC has not been well elucidated yet. In the present study, the results displayed the expression of hsa_circ_0030018 was dramatically increased in EC cells. Inhibition of has_circ_0030018 suppressed cell proliferation, migration, and epithelial-mesenchymal transition (EMT) process in EC. Based on molecular mechanism assays, has_circ_0030018 served as a sponge of miR-599. Enabled homolog (ENAH), which exhibited high expression in EC cells, was confirmed to be a downstream target gene of miR-599. Additionally, has_circ_0030018 positively regulated ENAH expression while miR-599 negatively regulated ENAH expression. Finally, by employing rescue assays, ENAH deficiency partially counteracted the promoting function of miR-599 silence on cell proliferation, migration, and EMT process in EC cotransfected with sh- has_circ_0030018#1 cells. In conclusion, hsa_circ_0030018 acted as a sponge of miR-599 to aggravate EC progression by regulating ENAH expression. Therefore, hsa_circ_0030018 might serve as a promising biomarker and therapeutic target for EC.     

Retracted: microRNA-539 functions as a tumor suppressor in papillary thyroid carcinoma via the transforming growth factor β1/Smads signaling pathway by targeting secretory leukocyte protease inhibitor

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, with growing incidence every year. microRNAs (miRs) are known to regulate the physiological and pathological processes of cancers, such as proliferation, migration, invasion, survival, and epithelial-mesenchymal transition (EMT). Herein, this study aimed to investigate the effect of miR-539 on cell proliferation, apoptosis, and EMT by targeting secretory leukocyte protease inhibitor (SLPI) via the transforming growth factor β1 (TGF-β1)/Smads signaling pathway in PTC. First, PTC-related differentially expressed genes and regulatory miR were screened using bioinformatics analysis, dual luciferase reporter gene assay, and ribonucleoprotein immunoprecipitation, which identified the SLPI gene and the regulatory miR-539 for this study. We identified SLPI as a highly expressed gene in PTC tissues, and SLPI was targeted and negatively regulated by miR-539. Then, we introduced a series of miR-539 mimics, miR-539 inhibitors, and small interfering RNA against SLPI plasmids into CGTHW-3 cells to examine the effects of miR-539 and SLPI on the expression of TGF-β1/Smads signaling pathway-, EMT-, and apoptosis-related factors, as well as cell proliferation, migration, invasion, and apoptosis. The obtained results indicated that CGTHW-3 cells treated with silenced SLPI or overexpressed miR-539 suppressed the cell proliferation, migration, invasion abilities, and resistance to apoptosis of PTC cells, corresponding to increased expression of Bcl-2-associated X protein, TGF-β1, Sekelsky mothers against dpp 4, and epithelial cadherin, and decreased B cell lymphoma 2, Vimentin, and N-cadherin. Altogether, we concluded that overexpressed miR-539 could inhibit the PTC cell proliferation and promote apoptosis and EMT by targeting SPLI via activation of the TGF-β1/Smads signaling pathway.     

CircATRNL1 increases acid-sensing ion channel 1 to advance epithelial-mesenchymal transition in endometriosis by binding to microRNA-103a-3p

Circular RNA ATRNL1 (circATRNL1) has been implicated in epithelial-mesenchymal transition (EMT) during endometriosis. Given the existing literature and our predictions through starBase in this research, it was assumed that circATRNL1 might orchestrate the microRNA (miR)? 103a-3p/acid-sensing ion channel 1 (ASIC1) axis to control EMT in endometriosis. To verify our hypothesis, we detect circATRNL1, miR-103a-3p, and ASIC1 expression in endometrial cancer cells (HEC-B, AN3-CA, KLE, HEC1-A, and Ishikawa). Ishikawa cells with the highest circATRNL1 level were selected as subjects, where circATRNL1, miR-103a-3p, or ASIC1 expression was knocked down. Scratch and Transwell assays were applied to assess cell migration and invasion, and CCK-8 and colony formation assays to detect cell proliferation. Western blot was used to measure E-cadherin, N-cadherin, Vimentin, and Slug expression to evaluate the EMT state. Furthermore, the binding of miR-103a-3p to circATRNL1 or ASIC1 was validated by luciferase reporter assay. CircATRNL1 and ASIC1 were upregulated but miR-103a-3p was downregulated in endometrial cancer cells. Mechanistically, circATRNL1 bound to miR-103a-3p to upregulate a target gene of miR-103a-3p, ASIC1. CircATRNL1 silencing contributed to the decline of proliferation, invasion, migration, and EMT in Ishikawa cells, while miR-103a-3p inhibitor reversed those changes. In addition, the EMT process was aggravated when miR-103a-3p was inhibited and this process was suppressed by silencing ASIC1 in the presence of downregulated miR-101a-3p. Our study supported that circATRNL1 might be a novel therapeutic candidate target for endometriosis treatment and provided unique insights into the molecular basis concerning the pathogenesis of endometriosis.     

Retracted: MicroRNA-373 promotes the development of endometrial cancer by targeting LATS2 and activating the Wnt/β-Catenin pathway

In the female reproductive tract, endometrial cancer is the most common malignant tumor. Recently, the specific functions of many miRNAs have been identified in endometrial cancer. However, the contradictory effects of microRNA-373 (miR-373) in different human cancers draw our attention. In the present research, upregulation of miR-373 was identified in endometrial cancer which predicted poor prognosis. Moreover, upregulation of miR-373 promoted the migration, invasion, and proliferation of endometrial cancer cells. To further confirm that results, the EMT and Wnt/β-Catenin pathways were also investigated, which were promoted by overexpression of miR-373. Then, we further investigate the downstream factor, large tumor suppressor kinase 2 (LATS2) which was inhibited by miR-373. LATS2 was verified as a direct target gene of miR-373 through luciferase reporter assay. Especially, the facilitation of miR-373 for cell proliferation, migration and invasion was impaired by LATS2. Taken together, miR-373 promotes the progression of endometrial cancer through targeting LATS2 and promoting EMT and Wnt/β-Catenin pathway.     

MiR-125b regulates the proliferation and metastasis of triple negative breast cancer cells via the Wnt/β-catenin pathway and EMT

Background/aim: MiR-125b plays an important role in breast cancer. The current study was to explore the expression and function of miR-125b in triple negative breast cancer cells. Materials and methods: The expression of miR-125b in human TNBC samples and cell lines were examined by qRT-PCR. MTT, scratch assays and transwell assays were utilized to observe the proliferation, migration and invasion ability. MiR-125b’s target gene and downstream signaling pathways were investigated by Luciferase Reporter Assays, qRT-PCR, immunofluorescence assays and western bolt. Results: MiR-125b was highly expressed in human TNBC tissues and cell lines. Inhibiting miR-125b expression suppressed the proliferation, cell migration and invasion. The three-prime untranslated region (3´-UTR) of adenomatous polyposis coli (APC) mRNA contains miR-125b binding sites, and inhibiting miR-125b expression suppressed the activity of the intracellular Wnt/β-catenin pathways and EMT. Conclusion: Inhibiting miR-125b regulates the Wnt/β-catenin pathway and EMT to suppress the proliferation and migration of MDA-MB-468 TNBC cells.     

MiR-4282 inhibits tumor progression through down-regulation of ZBTB2 by targeting LIN28B in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most aggressive type of head and neck cancer with an unsatisfactory 5-year survival rate. MicroRNAs are a group of small noncoding RNAs reported to serve important roles in carcinogenesis, inhibiting certain gene expression via targeting the 3′-untranslated region of messenger RNAs (mRNAs). MiR-4282 has been newly discovered to be a tumor suppressor in colorectal cancer, but it has never been studied in OSCC. The present study aimed to uncover the role of miR-4282 in OSCC. We first confirmed that miR-4282 was downregulated in OSCC and validated its prognostic significance. Through gain-of-function assays, miR-4282 was discovered to inhibit proliferation, migration, and epithelial-to-mesenchymal transition, and induce apoptosis. By mechanistic research, we predicted via bioinformatics tools and confirmed by luciferase reporter and pulldown assays that miR-4282 targeted LIN28B, an RNA-binding protein, which has been reported to regulate RNA stability in cancers. Furthermore, we confirmed the interaction between LIN28B and zinc finger and BTB domain containing 2 (ZBTB2), and validated that miR-4282 regulated mRNA stability of ZBTB2 by inhibiting LIN28B. Rescue assays proved that miR-4282 inhibited tumor progression through LIN28B/ZBTB2 axis. In vivo assays proved that miR-4282 inhibited tumor growth in OSCC. In conclusion, the present study revealed that miR-4282 inhibited tumor progression through downregulation of ZBTB2 by targeting LIN28B in OSCC cells, indicating miR-4282 as a novel biomarker for OSC.     

MicroRNA-497 inhibition of ovarian cancer cell migration and invasion through targeting of SMAD specific E3 ubiquitin protein ligase 1

Ovarian cancer is the leading cause of death from gynecological malignancies worldwide. Understanding the molecular mechanism underlying ovarian cancer progression facilitates the development of promising strategy for ovarian cancer therapy. Previously, we observed frequent down-regulation of miR-497 expression in ovarian cancer tissues. In this study, we investigated the role of miR-497 in ovarian cancer metastasis. We found that endogenous miR-497 expression was down-regulated in the more aggressive ovarian cancer cell lines compared with the less aggressive cells. Exogenous expression of miR-497 suppressed ovarian cancer cell migration and invasion, whereas reduction of endogenous miR-497 expression induced tumor cell migration and invasion. Mechanistic investigations confirmed pro-metastatic factor SMURF1 as a direct target of miR-497 through which miR-497 ablated tumor cell migration and invasion. Further studies revealed that lower levels of miR-497 expression were associated with shorter overall survival as well as increased SMURF1 expression in ovarian cancer patients. Our results indicate that down-regulation of miR-497 in ovarian cancer may facilitate tumor metastasis. Restoration of miR-497 expression may be a promising strategy for ovarian cancer therapy.     

miR-17-5p promotes proliferation and epithelial-mesenchymal transition in human osteosarcoma cells by targeting SRC kinase signaling inhibitor 1

MicroRNA-17-5p (miR-17-5p) and epithelial-mesenchymal transition (EMT) have been reported to participate in the development and progression of multiple cancers. However, the relationship between the miR-17-5p and EMT in osteosarcoma (OS) is still poorly understood. This study was to investigate the effects of the miR-17-5p and its potential mechanism in regulating proliferation, apoptosis, and EMT of human OS. Quantitative real-time PCR was used to detect the miR-17-5p and SRC kinase signaling inhibitor 1 (SRCIN1) messenger RNA expression in OS specimens and cell lines. After transfection with miR-17-5p inhibitors, proliferation, apoptosis, migration, and invasion of OS cells were assessed by using the Cell Counting Kit-8, the annexin V-FITC apoptosis, wound-healing, and transwell assays. The SRCIN1 was validated as a target of the miR-17-5p through bioinformatics algorithms and luciferase reporter assay. Moreover, the expression of EMT markers, E-cadherin, N-cadherin, and Snail was identified by the Western blot analysis. MiR-17-5p was significantly upregulated in OS tumor samples and cell lines. It inhibited proliferation and EMT, and promoted apoptosis in OS. The SRCIN1 was identified as a direct target of the miR-17-5p. Silenced miR-17-5p could change the expression of EMT markers, such as upregulating the expression of E-cadherin, and downregulating the expression of N-cadherin and Snail through targeting the antioncogenic SRCIN1. These findings suggest that the miR-17-5p promotes cell proliferation, and EMT in human OS by directly targeting the SRCIN1, and reveal a branch of the miR-17-5p/SRCIN1/EMT signaling pathway involved in the progression of OS.     

Eukaryotic initiation Factor 4AIII facilitates hepatocellular carcinoma cell proliferation,migration, and epithelial-mesenchymal transition process via antagonistically binding to WD repeat domain 66 with miRNA-2113

Hepatocellular carcinoma (HCC) is one of the malignant cancers with high incidence and mortality rates worldwide. RNA-binding protein eukaryotic initiation Factor 4A-III (eIF4AIII) is a carcinogene in the biological process of tumors and microRNA (miRNA)-2113 has rarely been studied in cancers, not to mention in HCC. The regulation mechanism between eIF4AIII and miR-2113 involved in HCC is yet to be explored. The purpose of this research is to probe the function role and associated underlying mechanism of eIF4AIII participated in HCC. The results revealed that eIF4AIII was overexpressed in HCC. Lost-of-function assays found that eIF4AIII knockdown, WD (Trp-Asp [tryptophan and asparaginic acid]) repeat domain 66 (WDR66) silence or miR-2113 promotion repressed cell proliferation, migration, and epithelial-mesenchymal transition (EMT) process in HCC. Furthermore, eIF4AIII could interact with WDR66 and further stabilize WDR66 messenger RNA. In addition, WDR66 was a target gene of miR-2113. Besides, WDR66 was antagonistically regulated by eIF4AIII and miR-2113. Rescue assays verified that eIF4AIII promoted HCC cell proliferation, migration, and EMT process via antagonistically binding to WDR66 with miR-2113. Taken together, these findings indicated an important role and a novel mechanism of eIF4AIII in HCC, providing an optional therapy for HCC patients.     

Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway

Sphingosine-1-phosphate (S1P) is a bioactive lipid known to play a role in tumorigenesis and cancer progression. However, the molecular mechanisms of S1P regulated migration of papillary thyroid cancer cells are still unknown. In this study, we showed that S1P induced PTK6 mRNA and protein expression in two thyroid follicular cancer cell lines (ML-1 and FTC-133). Further studies demonstrated that induced PTK6 and its downstream signal component (ERK1/2) are involved in S1P-induced migration. Upon investigating the mechanisms behind this event, we found that miR-17 inhibited the expression of PTK6 through direct binding to its 3’-UTR. Through overexpression and knockdown studies, we found that miR-17 can significantly inhibit S1P-induced migration in thyroid follicular cancer cells. Interestingly, overexpression or knockdown of PTK6 or ERK1/2 effectively removed the inhibition of S1P-induced migration by miR-17. Furthermore, we showed that S1P decreased miR-17 expression levels. Meanwhile, in papillary thyroid cancers, miR-17 is downregulated and negatively associated with clinical staging, whereas PTK6 is upregulated and positively associated with clinical stages. Collectively, our work defines a novel signaling pathway implicated in the control of thyroid cancer migration.     

microRNA-510-5p promotes thyroid cancer cell proliferation,migration, and invasion through suppressing SNHG15

SNHG15 has been suggested to be correlated with clinical progression and prognosis, and function as tumor suppressive long noncoding RNA in thyroid cancer at our previous study. SNHG15 was proposed to be a potential target for miR-510-5p at LncBase Predicted database. Thus, the aim of this study was to explore the relationship between miR-510-5p and SNHG15 in thyroid cancer, and the clinical significance of miR-510-5p in patients with thyroid cancer. In our results, levels of miR-510-5p expression were increased in thyroid cancer tissues and cell lines compared with adjacent normal thyroid tissues and normal thyroid cell line, respectively. There was a statistically negative correlation between SNHG15 expression and miR-510-5p expression in thyroid cancer tissues. Moreover, miR-510-5p directly bound to SNHG15, and negatively regulated SNHG15 expression in thyroid cancer cells. Furthermore, miR-510-5p promoted thyroid cancer cell proliferation, migration, and invasion through suppressing SNHG15. Finally, high miR-510-5p expression was observed in tumor tissues with advanced clinical stage or lymph node metastasis. In conclusion, we provide evidence to support a pivotal role for miR-510-5p in regulating thyroid cancer cell proliferation, migration, and invasion.     

Circular RNA TUBA1C accelerates the progression of non-small-cell lung cancer by sponging miR-143-3p

Non-small-cell lung cancer (NSCLC) is one of the most common solid tumors and the leading cause of lung cancer-related fatality. Growing evidence has indicated that circular RNAs (circRNAs) play important roles in the progression of multiple human cancers. As a novel circRNA, very little research has focused on the function of circRNA TUBA1C (circTUBA1C) in cancer development, including NSCLC. In the present study, we found that the expression of circTUBA1C was significantly upregulated in NSCLC tissues. The loss-of function assays suggested that circTUBA1C deficiency notably hampered cell proliferation as well as accelerated cell apoptosis in NSCLC. In mechanism, we discovered that circTUBA1C could act as a sponge for miR-143-3p and then negatively regulate miR-143-3p. Moreover, rescue assays demonstrated that knockdown of miR-143-3p could reverse circTUBA1C silence-mediated effects on cell proliferation and apoptosis. Besides, we established a xenografted tumor model to investigate the function of circTUBA1C in vivo. The result illustrated that the decline of tumor growth resulted from circTUBA1C deficiency could be recovered by miR-143-3p knockdown. Taken together, these findings indicated the important role of circTUBA1C/miR-143-3p axis in NSCLC, which may provide a potential target for NSCLC therapy.