Hsa_circRNA_0017620 regulated cell progression of non‐small‐cell lung cancer via miR‐520a‐5p/KRT5 axis

BackgroundCircRNA is a very important functional RNA that plays an important role in the development and metabolism of cancer. However, the study of circRNA in NSCLC has not been fully elucidated.MethodsThe expression of hsa_circ_0017620, SFMBT2, miR‐520a‐5p, and KRT5 was determined using qRT‐PCR. KRT5, Twist1, E‐cadherin, and Ki67 protein expression were measured with western blot. The positive expression rates of Ki67 and Vimentin were determined by immunohistochemistry assay. 5‐Ethynyl‐2’‐deoxyuridine (EdU), colony formation, and MTT assays were used to assess cell proliferation. Transwell migration and invasion assay were applied to determine cell migration and invasion. Dual‐luciferase reporter and RNA immunoprecipitation assays were used to verify the relationship among hsa_circ_0017620, miR‐520a‐5p, and KRT5. The animal experiment was used to ensure the effects of hsa_circ_0017620 on tumor growth in vivo.ResultsHsa_circ_0017620 was upregulated in NSCLC cells and tissues. MiR‐520a‐5p had been verified to be a target miRNA of hsa_circ_0017620 and KRT5 had been verified to be a target mRNA of miR‐520a‐5p in NSCLC cells. Knockdown of hsa_circ_0017620 inhibited cell proliferation, migration, and invasion in NSCLC cells, which was reversed by downregulating miR‐520a‐5p or upregulating KRT5 in NSCLC. Overexpression of hsa_circ_0017620 had opposite effects in NSCLC. Moreover, hsa_circ_0017620 silencing inhibited tumor growth in vivo of NSCLC.ConclusionIn this study, we found that hsa_circ_0017620 played an important role in NSCLC progression. Hsa_circ_0017620 regulated cell proliferation, invasion, and migration through targeting miR‐520a‐5p/KRT5 axis in NSCLC, providing a potential new target for the treatment and diagnosis of NSCLC.     

Hsa_circ_0092887 targeting miR‐490‐5p/UBE2T promotes paclitaxel resistance in non‐small cell lung cancer

BackgroundChemoresistance is a major contributing factor to cancer treatment failure. Emerging research reveals that circular RNA (circRNA) dysregulation is implicated in chemoresistance. Our current study aimed to investigate the involvement of hsa_circ_0092887 in paclitaxel (PTX) resistance in non‐small cell lung cancer (NSCLC).MethodsRT‐qPCR as well as western blotting were used for the analysis of hsa_circ_0092887, miR‐490‐5p and UBE2T expression in PTX‐resistant NSCLC tumor tissues and cells. CCK‐8 assay was done to determine the IC50 value of PTX. CCK‐8 assay, wound healing assay, analysis of apoptosis related proteins (Bax and Bcl‐2), and xenograft mouse models were utilized to investigate the role of hsa_circ_0092887 in PTX‐resistance in NSCLC. The binding sites of miR‐490‐5p to hsa_circ_0092887 or UBE2T were predicted by bioinformatics tools and were verified by RIP and dual‐luciferase assays.ResultsExpression of hsa_Circ_0092887 was upregulated in NSCLC tumor samples/cell lines, and its expression was also higher in PTX‐resistant tumor samples/cell lines when compared with their respective controls. Silencing of hsa_circ_0092887 in PTX‐treated NSCLC cells inhibited cell proliferation and migration, induced apoptosis, and suppressed tumor growth in xenograft mouse models in vivo. MiR‐490‐5p was a direct target of hsa_circ_0092887, and UBE2T was a functional downstream target of hsa_circ_0092887/miR‐490‐5p axis. Hsa_circ_0092887 depletion‐induced anti‐cancer effects in PTX‐treated NSCLC cells were reversed by miR‐490‐5p inhibitor. Furthermore, inhibition of miR‐490‐5p strengthened UBE2T expression, thereby attenuating the anti‐cancer effects caused by UBE2T knockdown.ConclusionHsa_circ_0092887 depletion alleviated PTX‐resistance in NSCLC cells via modulating the miR‐490‐5p/UBE2T axis, and the targeted management of hsa_circ_0092887‐mediated signaling axis might contribute to PTX‐resistance intervention in NSCLC.     

Hsa_circ_0002082 up‐regulates Centromere Protein F via abolishing miR‐508‐3p to promote breast cancer progression

BackgroundCircular RNAs (circRNAs) dysregulation has been revealed to function in the pathological processes of cancers. Herein, the role and mechanisms of hsa_circ_0002082 in breast cancer (BC) progression were elucidated.MethodsIn vivo and in vitro functional experiments were conducted, and the interaction between miR‐508‐3p and hsa_circ_0002082 or Centromere Protein F (CENPF) was elucidated.ResultsHsa_circ_0002082 expression was higher in BC tissues and cell lines. Functionally, knockdown of hsa_circ_0002082 induced apoptosis and suppressed proliferation and metastasis in BC cells in vitro. Mechanistically, hsa_circ_0002082 targeted miR‐508‐3p, which was confirmed to be decreased in BC. MiR‐508‐3p overexpression suppressed BC cell malignant phenotypes, moreover, inhibition of miR‐508‐3p attenuated the anticancer action of hsa_circ_0002082 silencing on BC cells. Besides that, miR‐508‐3p targeted CENPF, CENPF was highly expressed in BC, CENPF up‐regulation reversed the suppressive impacts of miR‐508‐3p on BC cell growth and metastasis. Besides, hsa_circ_0002082 silencing impeded BC growth in nude mice.ConclusionKnockdown of hsa_circ_0002082 suppresses breast cancer growth and metastasis by miR‐508‐3p/CENPF axis, suggesting that hsa_circ_0002082 may be a promising target for breast cancer treatment.     

Hsa_circ_0045932 regulates the progression of colorectal cancer by regulating HK2 through sponging miR‐873‐5p

BackgroundCircular RNAs (circRNAs) have been confirmed to be key regulators for colorectal cancer (CRC) progression. The purpose of this research was to explore the biological role and mechanism of hsa_circ_0045932 in CRC.MethodsRT‐qPCR and Western blot (WB) were applied to examine RNA and protein levels, respectively. MTT assay, EdU assay, and transwell assay were used to detect cell proliferative, migration, and invasion. Glucose uptake and lactic acid level were determined to assess cellular glycolysis. Dual‐luciferase reporter and RIP assays were carried out to detect the relationship between miR‐873‐5p and hsa_circ_0045932 or hexokinase 2 (HK2). Xenograft mice model was established to confirm the function of hsa_circ_0045932 in vivo.ResultsHsa_circ_0045932 was overexpressed in CRC tissue samples and cells. Hsa_circ_0045932 knockdown repressed CRC cell proliferation, invasion, migration, and glycolysis abilities in vitro. MiR‐873‐5p could be sponged by hsa_circ_0045932, and its inhibitor also reversed the inhibitory effect of hsa_circ_0045932 knockdown on CRC cell progression. HK2 was targeted by miR‐873‐5p, and hsa_circ_0045932 regulated HK2 expression through targeting miR‐873‐5p. Overexpression of HK2 reversed the repressive effect of hsa_circ_0045932 knockdown on CRC cell malignant behaviors. Furthermore, the pro‐tumor role of hsa_circ_0045932 in vivo was also confirmed using animal experiments.ConclusionHsa_circ_0045932 promoted CRC progression through sponging miR‐873‐5p to up‐regulate HK2, which might offer novel therapeutic target for CRC clinical intervention.     

LINC00240 knockdown inhibits nasopharyngeal carcinoma progress by targeting miR‐26a‐5p

ObjectiveThis study intended to explore the regulatory functions of LINC00240 on nasopharyngeal carcinoma (NPC).MethodsMiR‐26a‐5p inhibitor, mimic, and siLINC00240 were transfected into NPC cells. QRT‐PCR was employed to assess miR‐26a‐5p and LINC00240 expressions. The targeting relationship of LINC00240 and miR‐26a‐5p was analyzed through dual luciferase reporter and RNA immunoprecipitation assay. Cell counting kit‐8 assay, colony formation assay, flow cytometry assay, wound healing assay, Transwell assay and in vitro angiogenesis assay were adopted for the evaluation of the effects of LINC00240 or miR‐26a‐5p and LINC00240 on NPC cells regarding cell proliferation, apoptosis and cycle, migration, invasion, and angiogenesis. EZH2, cell cycle, and epithelial‐mesenchymal transition (EMT)‐related protein expression was tested through Western blot.ResultsLINC00240 had a high expression in NPC tissues and cell lines. Silenced LINC00240 significantly suppressed the 5‐8F and HK1 cell proliferation, invasion, migration, and angiogenesis, but raised cell apoptosis, and cells were blocked in G0/G1 phase. MiR‐26a‐5p was a target of LINC00240. MiR‐26a‐5p upregulation suppressed the NPC cell proliferation, migration, invasion, angiogenesis, N‐cadherin and EZH2 expression, while it elevated apoptosis and p21, p27 and E‐cadherin expressions, whereas miR‐26a‐5p downregulation performed conversely. LINC00240 knockdown partially offset the effects of miR‐26a‐5p downregulation on cell proliferation, migration, invasion, angiogenesis, apoptosis, and EZH2.ConclusionLINC00240 knockdown restrained cell proliferation, invasion, migration, and angiogenesis, while it advanced apoptosis via miR‐26a‐5p in NPC by EZH2 inhibition.     

Circular RNA hsa_circ_0043688 serves as a competing endogenous RNA for microRNA‐145‐5p to promote the progression of Keloids via Fibroblast growth factor‐2

BackgroundKeloids are benign fibroproliferative skin tumors. Circular RNA (circRNA) hsa_circ_0043688 has been exhibited to the freakishly expressed in keloid tissues. Here, we aimed to investigate the regulatory network of hsa_circ_0043688 in the pathological process of keloid.MethodsHsa_circ_0043688, microRNA‐145‐5p (miR‐145‐5p), and Fibroblast growth factor‐2 (FGF2) level were detected using RT‐qPCR. Cell viability, proliferation, apoptosis, invasion, and migration were investigated using Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays, respectively. Western blot analysis of protein levels of FGF2, CyclinD1, Collagen I, and Collagen III. After the prediction of Circinteractome and Starbase, their interaction was verified based on a dual‐luciferase reporter and RIP assays.ResultsIncreased hsa_circ_0043688 and FGF2, and decreased miR‐145‐5p in keloids samples and fibroblasts were found. Also, hsa_circ_0043688 absence hindered proliferation, invasion, migration, and boost apoptosis of keloid fibroblasts. In mechanism, hsa_circ_0043688 modulated FGF2 content via sponging miR‐145‐5p.ConclusionHsa_circ_0043688 knockdown inhibited cell growth and metastasis of keloid fibroblasts via miR‐145‐5p/FGF2, providing a new mechanism to understand the keloid progression.     

Circular RNA hsa_circ_0011298 enhances Taxol resistance of non‐small cell lung cancer by regulating miR‐486‐3p/CRABP2 axis

BackgroundCircular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non‐small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC.MethodsCirc_0011298, microRNA‐486‐3p (miR‐486‐3p), and CRABP2 mRNA expression were determined using qRT‐PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual‐luciferase reporter and RIP assays were performed to confirm the relationship between miR‐486‐3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo.ResultsCirc_0011298 was overexpressed in Taxol‐resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol‐resistant NSCLC cells. Circ_0011298 was a sponge of miR‐486‐3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR‐486‐3p inhibition. Moreover, miR‐486‐3p directly targeted CRABP2, and miR‐486‐3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR‐486‐3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo.ConclusionCirc_0011298 elevated Taxol resistance of NSCLC by sponging miR‐486‐3p and upregulating CRABP2, providing a possible circRNA‐targeted therapy for NSCLC.     

Hsa_circ_0005100 regulates tumorigenicity of colorectal carcinoma via miR‐145‐5p/ MACC1 axis

BackgroundCircular RNAs (circRNAs) are a kind of RNA molecules involved in the regulation of cancer progression, including colorectal carcinoma (CRC); nevertheless, their regulation mode is blurry. In the present work, we attempted to reveal the characteristics of hsa_hsa_circ_0005100 in CRC.MethodsDifferential expressions of hsa_circ_0005100, FMN2 mRNA, microRNA‐145‐5p (miR‐145‐5p), and MACC1 were indicated by qRT‐PCR and Western blot. The capacities of cell growth and motility were validated by the MTT assay, flow cytometry assay, EdU assay, colony formation assay, and transwell assay. Moreover, the targeted relationship of miR‐145‐5p and hsa_circ_0005100 or MACC1 was distinguished by dual‐luciferase reporter assay. The animal experiment was implemented to confirm the influence of hsa_circ_0005100 on tumorigenesis in vivo.ResultsHsa_circ_0005100 and MACC1 expression levels were increased, but miR‐145‐5p expression level was diminished in CRC. Hsa_circ_0005100 knockdown repressed cell proliferation, cell cycle, migration, and invasion, while expedited cell apoptosis in CRC cells. Furthermore, miR‐145‐5p was disclosed to block CRC via overturning MACC1. Hsa_circ_0005100 targeted miR‐145‐5p to modulate MACC1. Additionally, hsa_circ_0005100 knockdown also attenuated tumorigenesis in vivo.ConclusionHsa_circ_0005100 was a vital regulator in the development of CRC by miR‐145‐5p/MACC1 axis, which deepened the understanding of CRC pathogenesis from circRNA insights.     

Circ_0000463 contributes to the progression and glutamine metabolism of non‐small‐cell lung cancer by targeting miR‐924/SLC1A5 signaling

BackgroundCircular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non‐small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated.MethodsCell proliferation ability was analyzed by colony formation assay and 5‐ethynyl‐2’‐deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA‐924 (miR‐924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α‐ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth.ResultsCirc_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR‐924, and circ_0000463 interference‐mediated anti‐tumor effects were largely reversed by the silence of miR‐924 in NSCLC cells. miR‐924 interacted with the 3’ untranslated region (3’UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR‐924 overexpression‐mediated anti‐tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR‐924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo.ConclusionCirc_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR‐924/SLC1A5 axis.     

hsa_circ_0000285 facilitates thyroid cancer progression by regulating miR‐127‐5p/CDH2

Thyroid cancer (THCA) is a leading endocrine cancer and becomes the fifth most commonly diagnosed malignancy in females. It is confirmed that circular RNAs (circRNAs) perform regulatory potencies in the pathological progress of THCA. Our purpose was to certify the trait of hsa_circ_0000285 (circ_0000285) and investigate its modulatory mechanism in THCA progression. We identified the expression profile of hsa_circ_0000285 in THCA by conducting qRT‐PCR assay. Therewith, the potential of hsa_circ_0000285 in THCA development was determined with a set of functional experiments, including CCK‐8, wound healing assay, Western blot, and xenograft model. The molecular mechanism underlying hsa_circ_0000285 was investigated with bioinformatic analysis, RIP and dual‐luciferase reporter experiments. As opposed to normal samples and cells, hsa_circ_0000285 level was overtly increased in THCA specimens and cells. The downregulation of hsa_circ_0000285 weakened the proliferative and migratory capacity of THCA cells and promoted cell apoptosis. In addition, hsa_circ_0000285 silence suppressed the tumor growth of xenograft model mice in vivo. Notably, we demonstrated that hsa_circ_0000285 might target miR‐127‐5p/CDH2 axis in THCA. Afterward, our findings manifested that miR‐127‐5p attenuation blocked the function of hsa_circ_0000285 depletion in THCA cells. In the final step, CDH2 was proven to mediate the repressive potency of miR‐127‐5p in the malignant behaviors of THCA. Mechanistically, hsa_circ_0000285 induced the development of THCA via functioning as a competing endogenous RNA (ceRNA) of miR‐127‐5p to enhance CDH2 expression, which provided a new perspective for THCA therapy.     

Hsa_circ_0005529 promotes ZEB1 expression by regulating miR‐873‐5p and enhancing proliferation,invasion, and migration in gastric cancer cell lines

BackgroundGastric cancer is a relatively common tumor. As circular RNAs (circRNAs) are documented to modulate proliferation and metastasis in various cancers, we evaluated the functions of circRNAs, in particular, hsa_circ_0005529, in gastric cancer cells.MethodsLevels of hsa_circ_0005529 and miR‐873‐5p were examined by qRT‐PCR, and the presence of hsa_circ_0005529 was confirmed by RNase R treatment. CCK‐8, wound‐healing, and Transwell assays were used to assess proliferation, migration, and invasion, respectively, while Western blotting was used to determine levels of zinc finger E‐box‐binding homeobox 1 (ZEB1) and dual‐luciferase reporter assays to examine relationships between hsa_circ_0005529 and miR‐873‐5p.Resultshsa_circ_0005529 was strongly expressed in gastric cancer where it stimulated tumorigenic behavior. Furthermore, hsa_circ_0005529 was shown to promote ZEB1 expression by sponging miR‐873‐5p, an inhibitor of ZEB1 expression.ConclusionOur research showed that hsa_circ_0005529 promoted tumorigenic behavior in gastric cancer cells by adsorbing miR‐873‐5p to modulate ZEB1 levels. This suggests that hsa_circ_0005529 may be useful as a biomarker and target for diagnosing and treating gastric cancer.     

Hsa_circ_0058129 regulates papillary thyroid cancer development via miR‐873‐5p/follistatin‐like 1 axis

BackgroundPapillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. Circular RNAs (circRNAs) participate in regulating PTC. Here, we analyzed the role of hsa_circ_0058129 (circ_0058129) in PTC.MethodsThe expression of circ_0058129, fibronectin 1 (FN1) mRNA, microRNA‐873‐5p (miR‐873‐5p), and follistatin‐like 1 (FSTL1) was detected by qRT‐PCR and western blot. Cell proliferation was analyzed by CCK‐8, EdU, and flow cytometry analysis assays. Cell migration and invasion were evaluated by Transwell assay. The targeting relationship of miR‐873‐5p and circ_0058129 or FSTL1 was identified through dual‐luciferase reporter assay, RIP assay, and RNA pull‐down assay. Xenograft mouse model assay was implemented to determine the effect of circ_0058129 on tumor formation in vivo.ResultsThe circ_0058129 and FSTL1 abundances were increased, while the miR‐873‐5p content was decreased in PTC tissues and cells compared with control groups. Circ_0058129 shortage inhibited PTC cell proliferation, migration, and invasion. Moreover, miR‐873‐5p repressed PTC cell malignancy by binding to FSTL1. Circ_0058129 targeted miR‐873‐5p to regulate FSTL1.ConclusionCirc_0058129 expedited PTC progression through the miR‐873‐5p/FSTL1 pathway.     

Hsa_circ_0050102 regulates the pancreatic cancer development via miR‐218‐5p/PPME1 axis

BackgroundPancreatic cancer (PC) is a malignancy worldwide. Circular RNAs (circRNAs) affects the growth of PC, nonetheless the mechanism is blurry. Here, we reconnoitered the parts of hsa_circ_0050102 in PC.MethodsHsa_circ_0050102, microRNA‐218‐5p (miR‐218‐5p) and protein phosphatase methylesterase 1 (PPME1) abundances were indicated by quantitative RT‐PCR or Western blot. Moreover, the cell functions were uncovered. Additionally, the relation of miR‐218‐5p and hsa_circ_0050102 or PPME1 was identified by dual‐luciferase reporter assay. Ultimately, the mice teats were utilized to quantity the part of hsa_circ_0050102.ResultsHsa_circ_0050102 and PPME1 contents were increased, and the miR‐218‐5p was dwindled in PC. Hsa_circ_0050102 lack subdued cell vitality, colony formation, cell migration and invasion, and angiogenesis, but endorsed cell apoptosis in PC cells. Furthermore, miR‐218‐5p was established to block the development of PC cells via PPME1. Hsa_circ_0050102 bound to miR‐218‐5p to adjust the content of PPME1.ConclusionHsa_circ_0050102 expedited the expansion of PC through growing PPME1 abundance by adjusting miR‐218‐5p.     

LncRNA PITPNA‐AS1/miR‐223‐3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma

BackgroundLong noncoding RNAs (lncRNAs) are a kind of molecule that cannot code proteins, and their expression is dysregulated in diversified cancers. LncRNA PITPNA‐AS1 has been shown to act as a tumor promoter in a variety of malignancies, but its function and regulatory mechanisms in lung squamous cell carcinoma (LUSC) are yet unknown.MethodsThe mRNA and protein expression of genes were examined by RT‐qPCR, western blot, and IHC assay. The cell proliferation, migration, invasion, and stemness were detected through CCK‐8, colony formation, Transwell and spheroid formation assays. The CD44⁺ and CD166⁺‐positive cells were detected through flow cytometry. The binding ability among genes through luciferase reporter and RNA pull‐down assays. The tumor growth was detected through in vivo nude mice assay.ResultsThe lncRNA PITPNA‐AS1 had increased expression in LUSC and was linked to a poor prognosis. In LUSC, PITPNA‐AS1 also enhanced cell proliferation, migration, invasion, and stemness. This mechanistic investigation showed that PITPNA‐AS1 absorbed miR‐223‐3p and that miR‐223‐3p targeted PTN. MiR‐223‐3p inhibition or PTN overexpression might reverse the inhibitory effects of PITPNA‐AS1 suppression on LUSC progression, as demonstrated by rescue experiments. In addition, the PITPNA‐AS1/miR‐223‐3p/PTN axis accelerated tumor development in vivo.ConclusionsIt is the first time we investigated the potential role and ceRNA regulatory mechanism of PITPNA‐AS1 in LUSC. The data disclosed that PITPNA‐AS1 upregulated PTN through sponging miR‐223‐3p to enhance the onset and progression of LUSC. These findings suggested the ceRNA axis may serve as a promising therapeutic biomarker for LUSC patients.     

CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3

BackgroundLung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%–85% of non‐small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and regulatory mechanism of circRNA WHSC1 (circWHSC1) in NSCLC are unknown. Therefore, we aim to explore the function and mechanism of circWHSC1 in NSCLC oncogenesis and progression.MethodsqRT‐PCR was used for circWHSC1 level evaluation; Kaplan‐Meier was used for survival analysis; bioinformatics, dual‐luciferase activity, and RNA pull‐down were used for evaluating competing endogenous RNA (ceRNA) network; cell viability, colony formation, apoptosis, migration, and invasion were used for cell function analysis; function gain and loss with rescue experiments were used for exploring mechanism of circWHSC1 in NSCLC development.ResultsSignificantly up‐regulated circWHSC1 and down‐regulated microRNA‐296‐3p (miR‐296‐3p) were identified in NSCLC tissues and cells. Up‐regulated circWHSC1 was associated with poor prognosis in NSCLC patients. MiR‐296‐3p was sponged by circWHSC1, and AKT serine/threonine kinase 3 (AKT3) was target of miR‐296‐3p; meanwhile, miR‐296‐3p over‐expression significantly down‐regulated AKT3 expression, and co‐transfecting anti‐miR‐296‐3p rescued circWHSC1 silence caused AKT3 down‐regulation. CircWHSC1 silence significantly inhibited colony formation, viability, invasion, and migration, while increased NSCLC cell apoptosis, which were partially rescued by anti‐miR‐296‐3p.ConclusionCircWHSC1 is an independent indicator of poor prognosis in NSCLC patients, and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis. Targeting circWHSC1 might be a prospective strategy for diagnosis, therapeutics, and prognosis of NSCLC.     

MiR‐630 suppresses non‐small cell lung cancer by targeting vimentin

ObjectiveThis study aimed to clarify the function of miR‐630 on non‐small cell lung cancer (NSCLC) cells.MethodsQuantitative real‐time PCR was utilized to detect the mRNA expression of miR‐630 and vimentin (VIM) in NSCLC tissues and cells. The protein expression of VIM, P53, Caspase‐3, Bcl‐2, Bax and JAK2/STAT3 was evaluated via Western blot. Dual‐luciferase reporter assay was applied to evaluate whether VIM is the target gene of miR‐630. The migration, invasion, proliferation and apoptosis of NSCLC cells were examined by wound‐healing assay, transwell assay, CCK‐8 assay, and flow cytometry, respectively.ResultsMiR‐630 was lowly expressed in NSCLC tissues and cells, while VIM was highly expressed in NSCLC cells. Dual‐luciferase reporter assay data validated that miR‐630 directly targeted VIM. MiR‐630 overexpression inhibited VIM expression, but the inhibition of miR‐630 upregulated VIM expression. Besides, miR‐630 mimics restrained cell migration, invasion, and proliferation, and promoted NSCLC cell apoptosis. Whereas, VIM overexpression partly attenuated the inhibitory effect of miR‐630 on NSCLC cells. Moreover, miR‐630 mimics impeded p‐JAK2 and p‐STAT3 protein expression; and miR‐630 inhibitor upregulated p‐STAT3 and VIM protein expression, which was reversed after the addition of STAT3 inhibitor C188‐9.ConclusionMiR‐630 constrained the progression of NSCLC by inhibiting JAK2/STAT3 pathway and downregulating VIM expression.