Circ-U2AF1 promotes human glioma via derepressing neuro-oncological ventral antigen 2 by sponging hsa-miR-7-5p

The prognosis for human glioma, a malignant tumor of the central nervous system, is poor due to its rapid growth, genetic heterogeneity, and inadequate understanding of its underlying molecular mechanisms. Circular RNAs composed of exonic sequences, represent an understudied form of noncoding RNAs (ncRNAs) that was discovered more than a decade ago, function as microRNA sponges. We aimed to assess the relationship between circ-U2AF1 (CircRNA ID: hsa_circ_0061868) and hsa-mir-7-5p and examine their effects on proliferation, apoptosis, and the metastatic phenotype of glioma cells regulated by neuro-oncological ventral antigen 2 (NOVA2). We found that the expression levels of circ-U2AF1 and NOVA2 were upregulated, while hsa-miR-7-5p was downregulated in human glioma tissues and glioma cell lines. Our data and bioinformatic analysis indicated the association of these molecules with glioma grade, a positive correlation between circ-U2AF1 and NOVA2 expression levels and a negative correlation of hsa-miR-7-5p with both circ-U2AF1 and NOVA2, respectively. In addition, silencing of circ-U2AF1 expression resulted in increased hsa-miR-7-5p expression and decreased NOVA2 expression both in vitro and in vivo. Luciferase assay confirmed hsa-miR-7-5p as a direct target of circ-U2AF1 and NOVA2 as a direct target of hsa-miR-7-5p. Functionally, silencing of circ-U2AF1 inhibits glioma development by repressing NOVA2 via upregulating hsa-miR-7-5p both in vitro and in vivo. Thus, we assumed that circ-U2AF1 promotes glioma malignancy via derepressing NOVA2 by sponging hsa-miR-7-5p. Taken together, we suggest that circ-U2AF1 can be a prognostic biomarker and the circ-U2AF1/hsa-miR-7-5p/NOVA2 regulatory pathway may be a novel therapeutic target for treating gliomas.     

Hsa_circ_0087354通过hsa-miR-199-3p/SLC7A11调节MG-63细胞增殖及氧化还原状态

环状RNA(circular RNAs, circRNAs)是一类新型非编码RNA。已有研究表明,其在细胞氧化还原反应中发挥重要作用。在本文前期研究中,发现通过real-time PCR检测,hsa_circ_0087354与细胞的氧化还原状态密切相关。过表达hsa_circ_0087354后,活性氧1(reactive oxygen species1,ROS1)基因表达显著下降(P＜0.01),超氧化物歧化酶1(surperoxide dismutase1,SOD1)表达显著升高(P＜0.05);细胞内SOD和谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)活性以及谷胱甘肽(glutathione,GSH)浓度显著升高(P＜0.01),细胞增殖能力增强(P＜0.05)。生物信息学分析预测,hsa-miR-199-3p与hsa_circ_0087354和溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)存在结合位点,可能存在靶向调控关系。双荧光素酶报告基因结果证实了hsa-miR-199-3p与hsa_circ_0087354和SLC7A11之间的靶向调控关系。构建过表达hsa_circ_0087354质粒和ctrl质粒,合成hsa-miR-199a-3p、hsa-miR-199b-3p 和hsa-miR-NC mimics。通过Real-time PCR分析发现,转染hsa_circ_0087354后,hsa-miR-199-3p表达显著降低(P＜0.01),SLC7A11表达显著升高(P＜0.05)。转染hsa-miR-199-3p后,SLC7A11基因表达显著下降(P＜0.001),细胞内SOD和GPx活性以及GSH浓度显著降低(P＜0.01),细胞增殖能力下降(P＜0.05)。研究结果表明,hsa_circ_0087354通过吸附hsa-miR-199-3p,增强SLC7A11表达,促进氧化应激MG-63细胞增殖,降低氧化应激水平。     

Identification of novel dysregulated circular RNAs in early-stage breast cancer

Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non-coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular RNAs associated with early-stage breast cancer. RNA sequencing and two circRNA detection tools (find_circ and DCC) were used to understand the circRNA expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up-regulated in early-stage breast cancer tissues. Co-expression analysis identified four pairs of circRNA-miRNA (hsa_circ_0023990 : hsa-miR-548b-3p, hsa_circ_0016601 : hsa_miR-1246, hsa_circ_0001946 : hsa-miR-1299 and hsa_circ_0000117:hsa-miR-502-5p) having potential interaction. The miRNA target prediction and network analysis revealed mRNA possibly regulated by circRNAs. We have thus identified circRNAs of diagnostic implications in breast cancer and also observed circRNA-miRNA interaction which could be involved in breast cancer development.     

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.     

Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition

Glioma remains one of the most aggressive and lethal cancers in central nervous system. Temozolomide (TMZ) is the most commonly used chemotherapeutic agent in gliomas. However, therapeutic benefits of TMZ could be very limited and all patients would finally suffer from tumor progression as the tumors develop resistance to TMZ. In this study, we aim to investigate the underlying mechanism of chemoresistance in glioma cell line and to identify whether there is still a close link between epithelial-mesenchymal transition (EMT) and TMZ resistance in gliomas. The real-time RT-PCR and Western blotting were used to measure the expression of EMT markers in TMZ-resistant cells. The migration and invasion assays were conducted to detect the cell motility activity in TMZ-resistant cells. The transfection was used to down-regulate the Cdc20 expression. The student t-test was applied for data analysis. We established stable TMZ-resistant glioma cells and designated as TR. Our results revealed that TR cells exhibited a significantly increased resistance to TMZ compared with their parental cells. Moreover, TMZ-resistant cells had acquired EMT-like changes. For the mechanism study, we measured a significant increased expression of CDC20 and decreased expression of Bim in TR cells. Moreover, upon suppression of CDC20 by shRNA transfection, TR cells underwent a reverse of EMT features. Importantly, knockdown of CDC20 enhanced the drug sensitivity of TR cells to TMZ. Our results suggested that inactivation of CDC20 could contribute to the future therapy that possibly overcomes drug resistance in human cancers.     

LncRNA RP1-86C11.7 exacerbates the glioma progression and oncogenicity by hsa-miR-144-3p/TFRC signaling.

Glioblastoma (GBM) remains the most common and malignant tumor of the human central nervous system. Increasing evidence has highlighted that tumor cells with high transferrin receptor (TFRC) expression show advantages in growth. Long noncoding RNAs (lncRNAs) are related to glioma progression by mediating microRNAs (miRNAs). However, the underlying mechanism among TFRC, miRNA and lncRNA in GBM is limited. In the current study, we identified a new lncRNA-induced signaling mechanism that regulates the TFRC levels in GBM. The TFRC level was higher in glioma cell lines, and elevated TFRC expression promoted the proliferation and survival of glioma cells. Further study showed that hsa-miR-144a-3p bound to the 3′-UTR of TFRC mRNA and inhibited its expression, preventing the malignant properties of glioma cells, such as proliferation and survival. We also found that the lncRNA RP1-86C11.7 sponges hsa-miR-144-3p to suppress its protective role in glioma. RP1-86C11.7 overexpression in glioma cells elevated TFRC expression, increased the intracellular free iron level, and deteriorated oncogenicity, with a significant reduction in hsa-miR-144-3p. By contrast, silencing RP1-86C11.7 upregulated the hsa-miR-144-3p level, resulting in decreased TFRC expression and repressed glioma progression. However, the effect of silencing RP1-86C11.7 was reversed with simultaneous hsa-miR-144-3p inhibitor treatment: the TFRC level, intracellular iron level and proliferation in glioma cells increased. Mechanistically, our data indicated that RP1-86C11.7 exacerbates the malignant behavior of glioma through the hsa-miR-144-3p/TFRC axis. RP1-86C11.7 may be a potential biomarker or target to treat glioma in the future.     

LncRNA RP1-86C11.7 exacerbates the glioma progression and oncogenicity by hsa-miR-144-3p/TFRC signaling.

Glioblastoma (GBM) remains the most common and malignant tumor of the human central nervous system. Increasing evidence has highlighted that tumor cells with high transferrin receptor (TFRC) expression show advantages in growth. Long noncoding RNAs (lncRNAs) are related to glioma progression by mediating microRNAs (miRNAs). However, the underlying mechanism among TFRC, miRNA and lncRNA in GBM is limited. In the current study, we identified a new lncRNA-induced signaling mechanism that regulates the TFRC levels in GBM. The TFRC level was higher in glioma cell lines, and elevated TFRC expression promoted the proliferation and survival of glioma cells. Further study showed that hsa-miR-144a-3p bound to the 3′-UTR of TFRC mRNA and inhibited its expression, preventing the malignant properties of glioma cells, such as proliferation and survival. We also found that the lncRNA RP1-86C11.7 sponges hsa-miR-144-3p to suppress its protective role in glioma. RP1-86C11.7 overexpression in glioma cells elevated TFRC expression, increased the intracellular free iron level, and deteriorated oncogenicity, with a significant reduction in hsa-miR-144-3p. By contrast, silencing RP1-86C11.7 upregulated the hsa-miR-144-3p level, resulting in decreased TFRC expression and repressed glioma progression. However, the effect of silencing RP1-86C11.7 was reversed with simultaneous hsa-miR-144-3p inhibitor treatment: the TFRC level, intracellular iron level and proliferation in glioma cells increased. Mechanistically, our data indicated that RP1-86C11.7 exacerbates the malignant behavior of glioma through the hsa-miR-144-3p/TFRC axis. RP1-86C11.7 may be a potential biomarker or target to treat glioma in the future.     

Autophagy-associated circular RNA hsa_circ_0007813 modulates human bladder cancer progression via hsa-miR-361-3p/IGF2R regulation

Circular RNAs (circRNAs) drive several cellular processes including proliferation, survival, and differentiation. Here, we identified a circRNA hsa_circ_0007813, whose expression was upregulated in bladder cancer. High hsa_circ_0007813 expression was associated with larger tumor size, higher primary tumor T stage, and higher pathologic grade. Survival analysis showed that patients with high hsa_circ_0007813 expression levels had a poorer prognosis. Based on these findings from clinical tissue samples and cell lines, we assumed that hsa_circ_0007813 functioned a vital role in bladder cancer progression. Next, functional experiments revealed that knockdown of hsa_circ_0007813 inhibited proliferation, migration, and invasiveness of bladder cancer cells both in vitro and in vivo. Through extensive bioinformatic prediction and RNA pull-down assays, we identified hsa-miR-361-3p as a competing endogenous RNA of hsa_circ_0007813. Further bioinformatic studies narrowed targets to 35 possible downstream genes. We then found that knockdown of hsa_circ_0007813 led to altered cell autophagy, bringing our attention to IGF2R, one of the possible downstream genes. IGF2R was also known as cation-independent mannose-6-phosphate receptor (CI-M6PR), was discovered to participate in both autophagy and tumor biology. Regarding autophagy has a dominant role in the survival of tumor cells overcoming cellular stress and correlates with tumor progression, investigations were made to prove that hsa_circ_0007813 could regulate IGF2R expression via hsa-miR-361-3p sponging. The potential of hsa_circ_0007813 in regulating IGF2R expression explained its influence on cell behavior and clinical outcomes. Collectively, our data could offer new insight into the biology of circRNA in bladder cancer.Subject terms: Cancer metabolism, Bladder cancer, Macroautophagy, Cell growth, Cell invasion     

Inhibition of Casein Kinase II by CX-4945, But Not Yes-associated protein (YAP) by Verteporfin,Enhances the Antitumor Efficacy of Temozolomide in Glioblastoma

Overcoming temozolomide (TMZ) resistance in glioma cancer cells remains a major challenge to the effective treatment of the disease. Increasing TMZ efficacy for patients with glioblastoma (GBM) is urgently needed because TMZ treatment is the standard chemotherapy protocol for adult patients with glioblastoma. O⁶-methylguanine-DNA-methyltransferase (MGMT) overexpression is associated with TMZ resistance, and low MGMT is a positive response marker for TMZ therapy. Here, we used 3 glioma cell lines (SF767, U373, and LN229), which had different levels of TMZ sensitivity. We found TMZ sensitivity is positively correlated with MGMT expression and multidrug-resistance protein ABC subfamily G member 2 (ABCG2) in these cells. CK2-STAT3 signaling and Hippo-YAP signaling are reported to regulate MGMT expression and ABCG2 expression, respectively. We combined CK2 inhibitor CX-4945 and YAP inhibitor verteporfin with TMZ treatment. We found that CX-4945 but not verteporfin can sensitize TMZ-resistant cells SF767 to TMZ and that CX-4945 and TMZ combinational treatment was effective for glioma treatment in mouse models compared with TMZ alone.ImplicationsA combination of CK2 inhibitor with TMZ may improve the therapeutic efficiency of TMZ toward GBM with acquired resistance.     

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     

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.     

Systematic identification of lncRNAs and circRNAs-associated ceRNA networks in human lumbar disc degeneration

ABSTRACT

Lumbar disc degeneration (LDD) is a common cause of low back and neck pain. The molecular mechanisms underlying LDD, however, are unclear. Noncoding RNAs have been reported to participate in human diseases. We investigated a series of public datasets (GSE67566, GSE56081 and GSE63492) and identified 568 mRNAs, 55 microRNAs (miRNAs), 765 long noncoding RNAs (lncRNAs), and 586 circular RNAs (circRNAs) that were expressed differently in LDD than in normal discs. We constructed lncRNAs and circRNAs regulated competing endogenous RNAs (ceRNA) networks in LDD. Four lncRNAs, DANCR, CASK-AS1, SCARNA2, and LINC00638), and three circRNAs, hsa_circ_0005139, hsa_circ_0037858, and hsa_circ_0087890, were identified as key regulators of LDD progression. We found that hsa-miR-486-5p regulated the crosstalk among circRNA hsa_circ_0000189, lncRNA DANCR and 6 mRNAs, PYCR2, TOB1, ARHGAP5, RBPJ, CD247, SLC34A1. Gene ontology (GO) analysis demonstrated that these differently expressed lncRNAs and circRNAs were involved in cellular component organization or biogenesis, gene expression and negative regulation of metabolic processes. Our findings provide useful information for exploring new mechanisms for LDD and candidates for therapeutic targets.     

Temozolomide resistance in glioblastoma cells occurs partly through epidermal growth factor receptor-mediated induction of connexin 43

Glioblastoma Multiforme (GBM) is an aggressive adult primary brain tumor with poor prognosis. GBM patients develop resistance to the frontline chemotherapy, temozolomide (TMZ). As the connexins (Cx) have been shown to have a complex role in GBM, we investigated the role of Cx43 in TMZ resistance. Cx43 was increased in the TMZ-resistant low passage and cell lines. This correlated with the data in The Cancer Genome Atlas. Cx43 knockdown, reporter gene assays, chromatin immunoprecipitation assay, real-time PCR and western blots verified a role for Cx43 in TMZ resistance. This occurred by TMZ-resistant GBM cells being able to activate epidermal growth factor receptor (EGFR). In turn, EGFR activated the JNK-ERK1/2-AP-1 axis to induce Cx43. The increased Cx43 was functional as indicated by gap junctional intercellular communication among the resistant GBM cells. Cell therapy could be a potential method to deliver drugs, such as anti-EGF to tumor cells. Similar strategies could be used to reverse the expression of Cx43 to sensitize GBM cells to TMZ. The studies showed the potential for targeting EGF in immune therapy. These agents can be used in conjunction with stem cell therapy to treat GBM.     

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR-181a to modulate SIRT1 expression

Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR-181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real-time polymerase chain reaction results showed that the expression of miR-181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR-181a, and miR-181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR-181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR-181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR-181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR-181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR-181a, and SIRT1 may serve as potential therapeutic targets for glioma.     

LRIG1 dictates the chemo-sensitivity of temozolomide (TMZ) in U251 glioblastoma cells via down-regulation of EGFR/topoisomerase-2/Bcl-2

In the current study, we aimed to understand the potential role of leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) in TMZ-resistance of U251 glioma cells. We established TMZ-resistant U251 clones (U251/TMZ cells), which expressed low level of LRIG1, but high levels of epidermal growth factor receptor (EGFR), topoisomerase-2 (Topo-2) and Bcl-2. Depletion of LRIG1 by the targeted RNA interference (RNAi) upregulated EGFR/Topo-2/Bcl-2 in U251 cells, and the cells were resistant to TMZ. Reversely, over-expression of LRIG1 in U251 cells downregulated EGFR/Topo-2/Bcl-2 expressions, and cells were hyper-sensitive to TMZ. Our data suggested EGFR-dependent mammalian target of rapamycin (mTOR) activation was important for Topo-2 and Bcl-2 expressions in U251/TMZ cells. The EGFR inhibitor and the mTOR inhibitor downregulated Topo-2/Bcl-2 expressions, both inhibitors also restored TMZ sensitivity in U251/TMZ cells. Finally, inhibition of Topo-2 or Bcl-2 by targeted RNAi(s) knockdown or by the corresponding inhibitor re-sensitized U251/TMZ cells to TMZ, indicating that both Topo-2 and Bcl-2 were important for TMZ resistance in the resistant U251 cells. Based on these results, we concluded that LRIG1 inhibits EGFR expression and the downstream signaling activation, interferes with Bcl-2/Topo-2 expressions and eventually sensitizes glioma cells to TMZ.     

Circular RNA hsa_circ_0085131 is involved in cisplatin‐resistance of non‐small‐cell lung cancer cells by regulating autophagy

Non‐small‐cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we reported the role of hsa_circ_0085131 in NSCLC. In the present study, NSCLC tumor specimens exhibited a higher hsa_circ_0085131 level in comparison to para‐tumor samples. And the higher level of hsa_circ_0085131 was associated with recurrence and poorer survival of NSCLC. Moreover, hsa_circ_0085131 promoted cell proliferation and cisplatin (DDP)‐resistance. Furthermore, hsa_circ_0085131 regulated cell DDP‐resistance by modulating autophagy. Hsa_circ_0085131 acted as a competing endogenous RNA of miR‐654‐5p to release autophagy‐associated factor ATG7 expression, thereby promoting cell chemoresistance. In conclusion, hsa_circ_0085131 enhances DDP‐resistance of NSCLC cells through sequestering miR‐654‐5p to upregulate ATG7, leading to cell autophagy. Therefore, these findings advocate targeting the hsa_circ_0085131/miR‐654‐5p/ATG7 axis as a potential therapeutic option for patients with NSCLC who are resistant to DDP.