RETRACTED ARTICLE: Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer

Molecular and Cellular Biochemistry - MicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the...     

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.     

HOXC13-AS promotes breast cancer cell growth through regulating miR-497-5p/PTEN axis

Dysregulated long noncoding RNAs (lncRNAs) remains to be explored in tumorigenesis. LncRNA HOXC13 antisense RNA (HOXC13-AS) has been found as an oncogene in many cancers; however, the role of HOXC13-AS in breast cancer still elusive. In this study, the HOXC13-AS levels and its role in cell proliferation was first measured by real-time quantitative polymerase chain reaction, Cell Counting Kit-8 assay, and colony formation assay. It showed that HOXC13-AS was increased in breast cancer tissues compared with the adjacent normal tissues and upregulated HOXC13-AS promoted the growth of breast cancer cells. Then, we found that the miR-497-5p levels were downregulated in cancer tissues compared with the adjacent tissues and miR-497-5p suppressed breast cancer cell proliferation. Further study showed that HOXC13-AS could function as a “sponge” for miR-497-5p then suppress miR-497-5p expression. Moreover, we next identified that Phosphatase and Tensin homolog (PTEN) is the target of miR-497-5p. Overexpression of miR-497-5p by chemical mimics decreased the expression of PTEN, while downregulation of miR-497-5p by HOXC13-AS rescued the expression of PTEN. Finally, we showed that HOXC13-AS promoted the proliferation of breast cancer cells and tumor growth through miR-497-5p/PTEN axis in vitro and in vivo. Hence, we conclude that HOXC13-AS, which is significantly upregulated in breast cancers, promoted cell proliferation through the suppressed miR-497-5p and further upregulated PTEN.     

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_0003098 promotes bladder cancer progression via miR-377-5p/ACAT2 axis

Accumulating evidence has proven that circRNAs play vital roles in tumor progression. Nevertheless, the mechanisms underlying circRNAs in bladder cancer (BCa) remain largely unknown. The purpose of this study was to identify the role and investigate the potential molecular mechanisms of hsa_circ_0003098 in BCa. We confirmed that hsa_circ_0003098 expression was significantly upregulated in BCa tissues, of which expression was remarkably associated with poor prognosis. Functionally, overexpression of hsa_circ_0003098 promoted BCa cell proliferation, migration, and invasion in vitro as well as tumor growth in vivo. Mechanistically, hsa_circ_0003098 promoted upregulation of ACAT2 expression and induced cholesteryl ester accumulation via acting as a sponge for miR-377-5p. Thus, hsa_circ_0003098 plays an oncogenic role in BCa and may serve as a potential biomarker and therapeutic target for BCa.     

CircABCB10 promotes nonsmall cell lung cancer cell proliferation and migration by regulating the miR-1252/FOXR2 axis

Circular RNA (circRNA) is a key regulator in the development and progression of human cancers. Previous studies confirmed circRNA-0008717 (circABCB10) as an oncogene in osteosarcoma, but the regulatory effect of circABCB10 in nonsmall cell lung cancer (NSCLC) is still unclear. In the current study, we examined the expression of circABCB10 in different NSCLC cell lines. Bioinformatics analysis, Cell Counting Kit-8 assays, Transwell migration, fluorescein reporting experiments, and xenografts in mice were used to detect the effect of circABCB10 on NSCLC cell proliferation and migration in vitro and tumor growth in vivo. The results showed that the expression of circABCB10 in NSCLC cell lines was increased. Downregulation of circABCB10 suppressed NSCLC cell proliferation and migration by promoting microRNA miR-1252 expression and suppressing Forkhead box 2 (FOXR2). Fluorescein reporting experiments confirmed that circABCB10 expression increased FOXR2 levels by sponging miR-1252, and in vivo experiments found that knockdown of circABCB10 decreased tumor growth. These data suggested that circABCB10 acted as a tumor promoter through a novel miR-1252/FOXR2 axis, providing potential biomarkers and therapeutic targets for the management of NSCLC.     

RNPC1 inhibits non-small cell lung cancer progression via regulating miR-181a/CASC2 axis

Objectives

To study the roles and mechanisms of RNA binding protein RNPC1 in non-small cell lung cancer progression.

Results

RNPC1 and long non-coding RNA CASC2 expression levels were significantly downregulated in lung cancer tissues compared with normal adjacent tissues, and their expression levels were positively correlated. Functionally, overexpression of RNPC1 or CASC2 inhibited non-small cell lung cancer cells proliferation, migration and invasion, and promoted cells apoptosis. Mechanistically, RNPC1 was found to harbor binding sites on CASC2 and directly bound to CASC2, and increased CASC2 mRNA stability and expression. Notably, the promotive effects of RNPC1 on CASC2 expression were attenuated by miR-181a overexpression. Moreover, CASC2 3′UTR with mutated miR-181a binding sites did not respond to RNPC1 alteration. Finally, the inhibitory effects of RNPC1 overexpression were attenuated or even reversed by CASC2 knockdown or miR-181a overexpression.

Conclusions

RNA bind protein RNPC1 could inhibit non-small cell lung cancer progression by competitively binding to CASC2 with miR-181a.

     

Long noncoding MAGI2-AS3 promotes colorectal cancer progression through regulating miR-3163/TMEM106B axis

Colorectal cancer (CRC), is mostly derived from normal colon epithelial cells, and has been reported to be one of most common gastrointestinal malignancies globally. An increasing number of researchers have claimed that long noncoding RNAs (lncRNAs) exert significant functions in tumor progression. Nevertheless, the function of MAGI2-AS3 remains uncertain in CRC. The expression of MAGI2-AS3, miR-3163, and transmembrane protein 106B (TMEM106B) messenger RNA was examined by quantitative real-time polymerase chain reaction. Cell apoptosis was measured by caspase-3 activity test. Cell proliferation was tested by cell-counting kit 8 and 5-ethynyl-2′-deoxyuridine assays. Cell migration was detected by transwell assay. Western blot analysis examined the protein expression of TMEM106B. The expression of Ki-67 was evaluated by immunohistochemistry assay. The binding capacity between miR-3163 and MAGI2-AS3 (or TMEM106B) was studied by radioimmunoprecipitation and luciferase reporter assays. The expression of MAGI2-AS3 and TMEM106B was conspicuously upregulated whereas miR-3163 presented lower expression in CRC cells. MAGI2-AS3 deficiency facilitated cell apoptosis but hampered cell proliferation and migration. MAGI2-AS3 combined with miR-3163 and negatively regulated miR-3163 expression. In addition, the administration of sh-MAGI2-AS3 or miR-3163 mimics suppressed CRC cell growth in vivo. Subsequently, miR-3163 targeted TMEM106B and the transfection of sh-MAGI2-AS3 or miR-3163 mimics downregulated TMEM106B expression. Rescue assays verified that TMEM106B overexpression recovered the effects of MAGI2-AS3 inhibition on cell apoptosis, proliferation, and migration in CRC. MAGI2-AS3 drives CRC progression through regulating miR-3163/TMEM106B axis. This supplies innovative insights on the investigation of molecular mechanism in CRC progression.     

Long non-coding FAM201A accelerates the tumorigenesis and progression of colorectal cancer through miR-3163/MACC1 axis

Colorectal cancer (CRC) is the leading contributor to cancer-relevant deaths worldwide with severe incidence and mortality. An extensive body of evidence has demonstrated that lncRNA plays a critical role in the oncogenicity of CRC. Despite the oncogenic function of FAM201A in esophageal squamous cell cancer and non-small-cell lung cancer, the potential of FAM201A in CRC progression remains unknown. FAM201A expression level was significantly enhanced in CRC cells compared with normal cells. Further, functional experiments illustrated that knockdown of FAM201A restrained cell growth, stemness and promoted chemoresistance of CRC cells. By exploring molecular mechanism of FAM201A, we found that FAM201A acted as a sponge of miR-3163. More importantly, oncogene MACC1 was confirmed to be a direct target of miR-3163 and FAM201A modulated MACC1 expression level via competing for miR-3163. Subsequently, we testified that FAM201A exerted its role in the tumorigenesis and development of CRC through targeting miR-3163/MACC1. Animal assay certified that FAM201A expedited CRC cell growth in vivo. In conclusion, our study was the first to unveil that FAM201A promoted cell proliferation and CSC characteristics in CRC via regulation of the miR-3163/MACC1 axis, which provided clues for the clinical treatment of patients with this disease.     

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.     

Circ_0137287 suppresses cell tumroigenesis and aerobic glycolysis in papillary thyroid carcinoma through miR-183-5p/PPP2R2A axis

Cytotechnology - Circ_0137287 was found to be decreased in papillary thyroid cancer (PTC) tissues and related to aggressive clinicopathologic characteristics. However, the role and mechanism of...     

Long non-coding RNA HOXA-AS3 facilitates the malignancy in colorectal cancer by miR-4319/SPNS2 axis

Journal of Physiology and Biochemistry - Growing evidence has shown the oncogenic role of long non-coding RNA HOXA-AS3 in the progression of several types of cancers, while the effect of HOXA-AS3...     

FOXO3a inhibits the EMT and metastasis of breast cancer by regulating TWIST-1 mediated miR-10b/CADM2 axis

BackgroundBreast cancer is the most common malignancy and has been considered as a leading cause of cancer death in women. Exploring the mechanism of breast cancer metastasis is extremely important for seeking novel therapeutic strategies and improving prognosis.MethodsClinical specimens and pathological characteristics were collected for evaluating the expression of forkhead box class O 3a (FOXO3a) and twist-related protein 1 (TWIST-1) in breast cancer tissues. CCK-8 assay was used to analyze cell proliferation. Cell invasion and migration were assessed by transwell assays. The expression of FOXO3a, TWIST-1, miR-10b, CADM2, FAK, phosphor-AKT and the epithelial-mesenchymal transition (EMT)-related protein (N-cadherin, E-cadherin and vimentin) were analyzed by RT-qPCR, immunohistochemical staining, immunofluorescence assay or western blot, respectively. Xenograft mouse models were used to analyze the role of the FOXO3a in breast cancer.ResultsFOXO3a was down-regulated and TWIST-1 was up-regulated in breast cancer tissues. Overexpression of FOXO3a or knockdown of TWIST-1 suppressed the proliferation, invasion, migration and EMT of breast cancer cells. Overexpression of TWIST-1 could reverse the effect of FOXO3a on the proliferation, invasion, migration and EMT of breast cancer. Moreover, FOXO3a suppressed the growth and metastasis of breast cancer by targeting TWIST1 in vivo.ConclusionFOXO3a inhibited the EMT and metastasis of breast cancer via TWIST-1/miR-10b/CADM2 axis.     

CircKIF2A contributes to cell proliferation,migration, invasion and glycolysis in human neuroblastoma by regulating miR-129-5p/PLK4 axis

Molecular and Cellular Biochemistry - Multiple circular RNAs (circRNAs) have been identified to act as essential mediators in diverse human cancers. However, the roles of circRNAs in neuroblastoma...