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.     

Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR-136/SH2B1 axis

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Currently, an increasing evidence showed that circular RNAs (circRNAs) play important roles in tumor progression. However, the effects and underlying mechanisms of circRNAs in CRC progression remain unclear. In the present study, through circRNA high-throughput sequencing and quantitative real-time polymerase chain reaction, we identified that hsa_circ_0136666 was significantly overexpressed in CRC tissues and cell lines. High hsa_circ_0136666 expression was associated with poor overall survival of patients with CRC. In vitro function assays showed that hsa_circ_0136666 inhibition suppressed CRC cell proliferation, migration, invasion, and arrested CRC cells in the G0/G1 phase. Furthermore, we showed that hsa_circ_0136666 inhibition reduced CRC cell growth in vivo. Mechanistically, we revealed that hsa_circ_0136666 could increase SH2B1 expression via competitively binding miR-136 in CRC cells. In addition, SH2B1 overexpression could reverse the effects of hsa_circ_0136666 inhibition on CRC cell progression. In conclusion, our data suggested that hsa_circ_0136666 could promote CRC cell progression via the miR-136/SH2B1 axis, elucidating a novel approach to improve the effectiveness of CRC treatment.     

Hsa_circ_0076931 suppresses malignant biological properties,down-regulates miR-6760-3p through direct binding,and up-regulates CCBE1 in glioma

The function of circular RNAs (circRNAs) in gliomas is as yet unknown. The present study explored role of hsa_circ_0076931 in glioma. circRNA expression profiles were identified via RNA-seq followed by qRT-PCR validation in three pairs of glioma and normal brain tissues (NBT). The function of hsa_circ_0076931 was investigated in vitro using cell lines as well as in vivo using a xenograft tumor. Hsa_circ_0076931 was up-regulated by overexpression and an mRNA profile compared with wild-type was identified by RNA-seq. The relationship between miR-6760-3p and hsa_circ_0076931 or CCBE1 was confirmed via luciferase reporter or AGO2-RIP assays. A total of 507 circRNAs were identified in glioma tissues that were differentially expressed compared with that in NBT, and the sequencing data were deposited in BioProject (ID: PRJNA746438). Hsa_circ_0007694 and hsa_circ_0008016 were memorably increased whereas hsa_circ_0076931 and hsa_circ_0076948 decreased in glioma compared with those in NBT. Additionally, hsa_circ_0076931 expression was negatively correlated with histological grade. Overexpression of hsa_circ_0076931 inhibited proliferation, migration, and invasion while promoting apoptosis of glioma cells. A total of 4383 and 537 aberrantly expressed genes were identified between the hsa_circ_0076931-overexpressed and control groups in H4 and U118-MG cells, respectively; the sequencing data were deposited in BioProject (ID: PRJNA746438). These differentially expressed genes were mainly enriched in cancer-related pathways. In addition, elevated hsa_circ_0076931 levels induced the expression of CCBE1 while suppressing miR-6760-3p expression. miR-6760-3p can bind to hsa_circ_0076931. The experimental evidence supports using hsa_circ_0076931 as a marker for glioma and to help prevent malignant progression. The mechanism might be relevant to miR-6760-3p and CCBE1.     

Long noncoding RNA LINC00460 promotes carcinogenesis via sponging miR-613 in papillary thyroid carcinoma

Long intergenic noncoding RNA 460 (LINC00460) has been identified as a critical regulator for multiple types of cancers. However, the biological role and underlying mechanism in human papillary thyroid carcinoma (PTC) still remain unclear and need to be uncovered. This study was aimed to ascertain the biological role and molecular mechanism of LINC00460 in PTC progression. Our findings revealed that the level of LINC00460 was significantly upregulated in PTC tissues and cell lines, which was positively correlated with advanced tumor–node–metastasis (TNM) stage and lymph node metastasis. Cellular experiments exhibited that knockdown of LINC00460 decreased proliferative, migratory, and invasive abilities of PTC cells. Mechanism assays noted that knockdown of LINC00460 suppressed cell proliferation, migration, and invasion, and inhibited expression of sphingosine kinase 2 (SphK2, a target of miR-613) in PTC cells, at least in part, by regulating miR-613. These findings suggested that LINC00460 could function as a competing endogenous RNA to regulate SphK2 expression by sponging miR-613 in PTC. Targeting LINC00460 could be a promising therapeutic strategy for patients with PTC.     

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.Subject terms: Gastrointestinal cancer, Non-coding RNAs     

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.     

Hsa_circ_0007456 regulates the natural killer cell-mediated cytotoxicity toward hepatocellular carcinoma via the miR-6852-3p/ICAM-1 axis

Circular RNAs (circRNAs) is one type of important non-coding RNAs that participate in tumorigenesis and cancer progression. In our previous study, we performed a microarray analysis of circRNAs between the tumor tissues and the adjacent normal tissues of hepatocellular carcinoma (HCC) patients, and found that the circRNA hsa_circ_0007456 is significantly downregulated in the tumor tissues and correlated with the prognosis of HCC. We further investigated the relationship between the expression levels of hsa_circ_0007456 in HCC and the susceptibility of NK cells, and found that the expression levels of hsa_circ_0007456 in HCC cell lines significantly influenced their susceptibility to NK cells. Through a series of screening and validation, we found that hsa_circ_0007456 mainly functioned through sponging miR-6852-3p and regulating the expression of intercellular adhesion molecule-1 (ICAM-1) in HCC. The miR-6852-3p/ICAM-1 axis is essential for the NK cytotoxicity toward HCC mediated by hsa_circ_0007456. In conclusion, we identify here hsa_circ_0007456 as a promising biomarker of HCC, and highlight hsa_circ_0007456/miR-6852-3p/ICAM-1 axis as an important signaling pathway in the process of tumor immune evasion and the tumorigenesis of HCC.Subject terms: Tumour biomarkers, Liver cancer     

miR-125a-3p suppresses the growth and progression of papillary thyroid carcinoma cell by targeting MMP11

The dysregulation of miR-125a-3p has been observed in multiple tumor types. Nevertheless, the function of miR-125a-3p in papillary thyroid carcinoma (PTC) is yet to be explored. Herein, we find that miR-125a-3p is markedly downregulated in PTC tissues, and its level is inversely related to the histological grade of PTC. Upregulation of miR-125a-3p suppresses the pulmonary metastatic ability as well as the tumor growth of PTC cell in vivo. Consistently, the colony formation ability and other metastasis-related traits of PTC cell are inhibited by miR-125a-3p transfection in vitro. In addition, we identify that matrix metalloprotease 11 (MMP11) is the direct target gene of miR-125a-3p, and that miR-125a-3p inhibits cell viability, migration, and invasiveness of PTC cell by reducing MMP11 expression in vitro. Together, these data testify that the miR-125a-3p/MMP11 axis plays vital roles in the growth and progression of human PTC cells.     

Circular RNA hsa_circ_0004015 regulates the proliferation,invasion, and TKI drug resistance of non-small cell lung cancer by miR-1183/PDPK1 signaling pathway

Circular RNAs (circRNAs) were recently reported to be involved in the pathogenesis of Non-small cell lung cancer (NSCLC), however, the molecular mechanisms of circRNAs in cell proliferation, invasion and TKI drug resistance remain largely undetermined. Here, we identified hsa_circ_0004015 was upregulated in NSCLC tissues, and was associated with the poor overall survival rate of NSCLC patients. Knockdown of hsa_circ_0004015 significantly decreased cell viability, proliferation, and invasion, whereas overexpression exhibited opposed effects in vivo and in vitro. Furthermore, hsa_circ_0004015 could enhance the resistance of HCC827 to gefitinib. In mechanism, hsa_circ_0004015 acted as a sponge for miR-1183, and PDPK1 was revealed to be target gene of miR-1183. Subsequently, functional assays illustrated that the oncogenic effects of hsa_circ_0004015 was attributed to the regulation of miR-1183/PDPK1 axis. In conclusion, circ_0016760/miR-1183/PDPK1 signaling pathway might play vital roles in the tumorigenesis of NSCLC.     

Hsa_circ_0001495 contributes to cervical cancer progression by targeting miR-526b-3p/TMBIM6/mTOR axis

Cervical cancer (CC) is a common gynecological malignant tumor, causing poor survival rate. Circular RNAs (circRNAs) are abundantly expressed in CC with their stable loop structure. However, the underlying mechanism and biological function of circRNAs remained unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay, we measured the expression of hsa_circ_0001495, miR-526b-3p, and transmembrane Bax inhibitor motif containing 6 (TMBIM6) in CC tissues and cells. The relationship between miR-526b-3p and hsa_circ_0001495 or TMBIM6 was investigated by bioinformatics analysis, dual-luciferase and RIP analysis. Enzyme linked immunosorbent assay (ELISA) was conducted to evaluate glucose consumption and lactate production. 5-ethynyl-2′-deoxyuridine (EDU) assay were used to test cell proliferation. Cell apoptosis was analyzed by using flow cytometry assay. Transwell and wound-healing assays were used to measure cell invasion and migration. The expression of proteins was examined by western blot. Xenograft assay was applied to detect the effect of hsa_circ_0001495 in vivo. Our finding showed that hsa_circ_0001495 and TMBIM6 expression were upregulated, while miR-526b-3p was downregulated in CC tissues and cell lines. Hsa_circ_0001495 knockdown or TMBIM6 knockdown suppressed cell proliferation, migration, glycolysis, while promoted cell apoptosis in vitro, and hsa_circ_0001495 silence curbed tumor growth in vivo. Beside, hsa_circ_0001495 exerted its function in CC by positively regulating TMBIM6. Furthermore, hsa_circ_0001495 acted as a sponge for miR-526b-3p to regulate TMBIM6 expression. Hsa_circ_0001495/miR-526b-3p/TMBIM6 axis also regulated the phosphorylation of mammalian target of rapamycin (mTOR) in CC cells. In summary, hsa_circ_0001495 regulated the progression of CC by regulating miR-526b-3p/TMBIM6/mTOR pathway.     

Hsa_circ_0136666 activates Treg-mediated immune escape of colorectal cancer via miR-497/PD-L1 pathway

PurposeIn the rankings of cancer mortality and incidence worldwide, colorectal cancer ranks fourth and the third, respectively. Circular RNA hsa_circ_0136666 (hsa_circ_0136666) is reported to participate in the growth of colorectal cancer. However, the mechanism by which hsa_circ_0136666 regulates the tumorigenesis of colorectal cancer needs to be further explored. In this study, we report here the role of hsa_circ_0136666 in the aberrant activation of Treg cells and immune evasion of tumor cells, providing a new strategy for the treatment of colorectal cancer.MethodsWestern blotting assay and qRT-PCR assay were used to determine protein and mRNA expression levels. Dual-luciferase reporter assay was used to evaluate the targeted regulatory relationship. RNA immunoprecipitation was used to detect RNA binding. Colony formation assay was utilized to measure the cell proliferation. Flow cytometry was used to assess cell apoptosis. Xenograft model was setup to evaluate tumor growth.ResultsThe results showed that hsa_circ_0136666 and PD-L1 was increased in colorectal cancer cells while miR-497 was decreased in colorectal cancer cells when compared with normal colon epithelial cell line. Hsa_circ_0136666 was demonstrated to directly target miR-497, which also regulated PD-L1 by binding to its 3′UTR. Further mechanistic studies identified that hsa_circ_0136666 controlled cell proliferation and apoptosis via targeting miR-497 and regulating PD-L1 expression. Of note, hsa_circ_0136666 stimulated Treg cells mediated by miR-497/PD-L1 axis and its downstream signal pathway in Treg cells. Finally, hsa_circ_0136666 was found to accelerate the tumor growth in vivo.ConclusionsOur findings demonstrated that hsa_circ_0136666 promoted the expression of PD-L1 by inhibiting miR-497 level in colorectal cancer, thus inducing the activation of Treg cells and leading to the immune escape of tumor, providing a novel mechanistic insight into the pathogenesis of colorectal cancer.     

Hsa_circ_0092276 promotes doxorubicin resistance in breast cancer cells by regulating autophagy via miR-348/ATG7 axis

Previous study has confirmed that hsa_circ_0092276 is highly expressed in doxorubicin (DOX)-resistant breast cancer cells, indicating that hsa_circ_0092276 may be involved in regulating the chemotherapy resistance of breast cancer. Here we attempted to investigate the biological role of hsa_circ_0092276 in breast cancer. We first constructed DOX-resistant breast cancer cells (MCF-7/DOX and MDA-MB-468/DOX). The 50% inhibiting concentration of MCF-7/DOX and MDA-MB-468/DOX cells was significantly higher than that of their parental breast cancer cells, MCF-7 and MDA-MB-46. MCF-7/DOX and MDA-MB-468/DOX cells also exhibited an up-regulation of drug resistance-related protein MDR1. Compared with MCF-7 and MDA-MB-46 cells, hsa_circ_0092276 was highly expressed in MCF-7/DOX and MDA-MB-468/DOX cells. Hsa_circ_0092276 overexpression enhanced proliferation and the expression of LC3-II/LC3-I and Beclin-1, and repressed apoptosis of breast cancer cells. The effect of hsa_circ_0092276 up-regulation on breast cancer cells was abolished by 3-methyladenine (autophagy inhibitor). Hsa_circ_0092276 modulated autophagy-related gene 7 (ATG7) expression via sponging miR-384. Hsa_circ_0092276 up-regulation promoted autophagy and proliferation, and repressed apoptosis of breast cancer cells, which was abolished by miR-384 overexpression or ATG7 knockdown. In addition, LV-circ_0092276 transfected MCF-7 cell transplantation promoted autophagy and tumor growth of breast cancer in mice. In conclusion, our data demonstrate that hsa_circ_0092276 promotes autophagy and DOX resistance in breast cancer by regulating miR-348/ATG7 axis. Thus, this article highlights a novel competing endogenous RNA circuitry involved in DOX resistance in breast cancer.     

Hsa_circ_0000119 promoted ovarian cancer development via enhancing the methylation of CDH13 by sponging miR-142-5p

Ovarian cancer is the leading cause of gynecological cancer-related death in women, and is difficult to treat. The aim of our study is to explore the role and action mechanism of hsa_circ_0000119 in ovarian cancer, thus to analyze whether the circular RNA is a potential target for the treatment of the disease. In this present study, our data shows that hsa_circ_0000119 and DNA methyltransferase 1 (DNMT1) was increased, while miR-142-5p was decreased in ovarian cancer. Overexpression of hsa_circ_0000119 promoted tumor growth, while silencing of hsa_circ_0000119 resulted in an opposite effects. Decreasing of hsa_circ_0000119 also notably inhibited the proliferation, migration, and invasion of the ovarian cancer cells. Moreover, the data proves that hsa_circ_0000119 negatively regulated miR-142-5p and cadherin 13 (CDH13) expression, but positively regulated DNMT1 expression. miR-142-5p could interact with hsa_circ_0000119 and DNMT1 3′-UTR. Silencing of DNMT1 could reverse the inhibition of hsa_circ_0000119 to miR-142-5p and CDH13 expression. Importantly, higher level of CDH13 promoter methylation existed in the ovarian tumors than that in matched normal tissues. DNA methyltransferase inhibitor could increase the expression of CDH13 in ovarian cancer cells. In addition, our results also prove that increasing of CDH13 or miR-142-5p effectively reversed the inhibition of hsa _circ_0000119 to the cell malignant phenotypes. Overall, our data demonstrate that hsa_circ_0000119 facilitated ovarian cancer development through increasing CDH13 expression via promoting DNMT1 expression by sponging miR-142-5p. Our data demonstrate the potential role of hsa_circ_0000119 in the treatment of ovarian cancer.     

Circular RNA hsa_circ_0001564 regulates osteosarcoma proliferation and apoptosis by acting miRNA sponge

Circular RNAs (circRNAs) is a novel type of non-coding RNAs generated from back splicing, which has been verified to mediate multiple tumorigenesis. However, the role of circRNA in osteosarcoma is still unclear. In the present study, we preliminarily screened the circRNAs expression profiles in osteosarcoma and investigated the potential regulation mechanism. The circRNAs expression profiles in osteosarcoma were screened using circRNA microarray analysis, and results showed that there were 1152 circRNAs up-regulated and 915 circRNAs down-regulated in tumor tissue compared to adjacent tissue. Hsa_circ_0001564, located at 5q35.3 and its associated-gene symbol is CANX, was one of the significantly overexpressed circRNAs in osteosarcoma tissue, as well as in osteosarcoma cell lines. In functional experiments, hsa_circ_001564 knockdown significantly suppressed the proliferation activity, induced cell cycle arrest in G0/G1 phase, and promoted apoptosis in HOS and MG-63 cells. Subsequently, we explored the probable mechanism of hsa_circ_001564, and fortunately, bioinformatics analysis revealed that miR-29c-3p contained the complementary binding region with hsa_circ_0001564, which was confirmed by dual-luciferase reporter assay. Moreover, rescue experiments illustrated that miR-29c-3p could reverse the oncogenesis effect of hsa_circ_001564. Our study discovers that hsa_circ_0001564 acts as miR-29c-3p sponge to mediate the tumorigenicity, which could act as a potential biomarker for the osteosarcoma and provide a novel insight for competing endogenous RNAs (ceRNAs) mechanism in osteosarcoma.     

Hsa_circ_0003596 enhances the development of cell renal clear cell carcinoma through the miR-502-5p/IGF1/PI3K/AKT axis

Accumulating research findings have shown that circular RNAs (circRNAs) play an indispensable role in tumorigenesis and tumor progression. The current study aimed to explore the role and modulatory mechanism of hsa_circ_0003596 in clear cell renal cell carcinoma (ccRCC). Quantitative real-time polymerase chain reaction was adopted to detect the expression of hsa_circ_0003596 in ccRCC tissue and cell lines. 5-Ethynyl-2′-deoxyuridine, cell counting kit 8 and the colony formation assay were utilized to assess the proliferation potential of the ccRCC cells. Transwell along with wound healing assays were adopted to quantify infiltration coupled with the migration potential of the cells. The current research study found that the circRNA hsa_circ_0003596 was overexpressed in ccRCC tissue and cell lines. Further, result showed that hsa_circ_0003596 was associated with distant metastasis of renal cancer. Notably, the knockdown of hsa_circ_0003596 can lower the proliferation, infiltration and migration potential of ccRCC cells. The results of in vivo experiments found that the reduction of hsa_circ_0003596 significantly hampered the growth of tumors in mice. In addition, it was evident that hsa_circ_0003596 acts as a “molecular sponge” for miR-502-5p to upregulate the expression of the microRNA-502-5p (miR-502-5p) target insulin-like growth factor 1 (IGF1R). Furthermore, it was found that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling was the downstream cascade of hsa_circ_0003596/miR-502-5p/IGF1R cascade, which is partly responsible for the cancer-promoting effect. Overall, the results of the present study showed that hsa_circ_0003596 facilitated the proliferation, infiltration and migration of ccRCC through the miR-502-5p/IGF1R/PI3K/AKT axis. Therefore, it was evident that hsa_circ_0003596 can serve as a possible biomarker and therapeutic target against ccRCC.     

Retracted: Long non-coding RNA LINC00152 promotes cell growth and invasion of papillary thyroid carcinoma by regulating the miR-497/BDNF axis

Long intergenic non-coding RNA 152 (LINC00152) was reported to be tightly linked to tumorigenesis and progression in multiple cancers. However, its biological role and modulatory mechanism in papillary thyroid carcinoma (PTC) has not been elucidated. In this study, we determined the expression levels of LINC00152 in PTC tissues and cell lines by quantitative real time polymerase chain reaction (qRT-PCR). Cell proliferation, colony formation, migration, and invasion were measured by a Cell Counting Kit-8 assay, colony formation analysis, wound healing, and transwell invasion assay, respectively. A luciferase reporter assay and qRT-PCR were used to determine whether LINC00152 interacts with miR-497 directly. We established a xenograft mouse model to examine the underlying molecular mechanism and effect of LINC00152 on tumor growth in vivo. We found that LINC00152 expression was significantly increased in PTC tissues and derived cell lines. LINC00152 knockdown significantly inhibited proliferation, colony formation, migration, and invasion in vitro, and impaired tumor growth in vivo. We revealed that LINC00152 functioned as a competing endogenous RNA to the miR-497 sponge, downregulating its downstream target brain-derived neurotrophic factor (BDNF), which is an oncogene in thyroid cancer. These findings suggest that LINC00152 is responsible for PTC cell proliferation and invasion and exerts its function by regulating the miR-497/BDNF axis.     

Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p

Circular RNA (circRNA) is a new class of noncoding RNA, and plays an important role in many pathological processes. Cervical cancer is the most common gynecologic malignant tumor. Recently, studies have shown that there is a variety of circRNA involved in the pathogenesis of cervical cancer. We screened out the highly expressed hsa_circ_0000263 from GSE102686 by the quantitative real-time polymerase chain reaction assay in cervical cancer cell lines. In this study, we investigated whether hsa_circ_0000263 might affect cell proliferation, migration, cell cycle and apoptosis in cervical cancer in vitro and in vivo. The luciferase reporter assay and RNA immunoprecipitation assay confirmed the direct interaction between miR-150-5p and hsa_circ_0000263. By using western blot and immunohistochemistry, we confirmed that hsa_circ_0000263 can regulate the expression of murine double minute 4 (MDM4) by affecting miR-150-5p, and finally affect the expression of p53 gene. We found that hsa_circ_0000263 was significantly upregulated in cervical cancer cells. In addition, the knockdown of hsa_circ_0000263, would inhibit cell proliferation and migration ability. In conclusion, our current research reveals the important role of hsa_circ_0000263/miR-150-5p/MDM4/p53 regulatory network in cervical cancer and provides a new insight into the pathogenesis of cervical cancer.     

miR-206 inhibits thyroid cancer proliferation and invasion by targeting RAP1B

Thyroid cancer (TC) is one of the primary tumors arisen from endocrine system. The purpose of this study was to investigate the underlying mechanism by which RAP1B (Ras-related protein Rap-1b) modulates microRNA (miR)-206 related effects on TC cells. Expression of miR-206 and RAP1B was analyzed in cells and tissues. miR-206 mimics or inhibitors and RAP1B vector were used in functional experiments to investigate the effects of miR-206 and RAP1B on cell activities including proliferation, migration, and invasion. Luciferase assay was performed to explore the association between miR-206 and RAP1B. The influence of miR-206 on tumorigenesis of TC cells was investigated using an ex vivo model. Our results demonstrated the reduce of miR-206 in TC tissues and cell lines in which RAP1B was increased. Overexpression of miR-206 significantly inhibited the functional capacities of TPC-1 cells including proliferation, invasion, and migration, most likely, through reducing the expression of RAP1B. Xenograft experiment showed that increased miR-206 could effectively inhibit the tumorigenesis of TC cells. Our study showed that miR-206 negatively regulated cell activities of proliferation, invasion, and migration in TC via suppressing RAP1B expression, suggesting that miR-206 exerts a vital role in TC.