LINC00601 promotes the progression of glioma via the p-STAT3 signaling pathway

doi:10.21203/rs.3.rs-4952967/v1

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Research Article

LINC00601 promotes the progression of glioma via the p-STAT3 signaling pathway

https://doi.org/10.21203/rs.3.rs-4952967/v1

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Background

Gliomas, the most common malignant tumors of the central nervous system, primarily originate from glial cells, which support nerve cells. Due to their high malignancy and aggressiveness, gliomas frequently result in poor prognoses. Increasing evidence suggests that long non-coding RNAs (lncRNAs) have diverse roles in cancer; however, their specific functions in gliomas remain poorly understood. This study elucidates the roles and potential mechanisms of the lncRNA LINC00601 in glioma.

Methods

Bioinformatics analysis was utilized to identify the expression of LINC00601 and to perform related survival analysis. Glioma cells were transfected with a control vector small interfering RNA (si-NC) or small interfering RNA LINC00601 (si-LINC00601). Cell proliferation was evaluated using the CCK-8 assay and plate colony formation assay. Cell migration and invasion were assessed using the Transwell assay. Protein expression was detected by Western blot analysis, and lncRNA levels were measured using quantitative real-time PCR (qRT-PCR).

Results

Bioinformatics analysis revealed that LINC00601 is associated with the pathological grade and prognosis of glioma, as evidenced by data from the TCGA and CGGA databases. In vivo experiments showed that LINC00601 knockdown inhibits the proliferation, migration, and invasion of U251 and U87 cells. Based on sequencing and Western blot results, this effect is thought to be linked to changes in Phosphorylated Signal Transducer and Activator of Transcription 3 (p-STAT3) expression. Additionally, in vitro knockdown of LINC00601 has been shown to inhibit glioma growth.

Conclusions

LINC00601, which facilitates glioma progression by modulating the p-STAT3 signaling pathway, could serve as a potential molecular target for glioma therapy.

glioma

lncRNA

LINC00601

p-STAT3

Glioma is the most common intracranial malignancy, accounting for 80% of malignant brain tumors and 30% of brain tumors [1]. They are classified into several types: diffuse astrocytomas, oligodendrogliomas, other astrocytomas, ependymomas, mixed glial tumors, and other gliomas [2]. The annual incidence of glioma is approximately 6.04 cases per 100,000 people [3]. Although this rate is not high, the mortality rate is extremely high, warranting classification as "extremely dangerous." Owing to its invasive growth characteristics, the efficacy of surgical treatment for malignant glioma is severely limited; patients' postoperative survival time typically ranges from 12 to 15 months. Most patients die within two years, and the five-year survival rate is less than 5% [4]. Although new techniques and advances in research have significantly improved the clinical diagnosis, evaluation, treatment, and prognosis of glioma [5], most glioma patients exhibit resistance to radiotherapy and chemotherapy [6]. This resistance leads to treatments that can only partially delay the recurrence of glioma and prolong survival times; however, the therapeutic outcomes for some malignant glioma patients remain poor [7]. Therefore, the highly aggressive growth of gliomas has attracted increasing attention [8]. The search for effective molecular biological markers for glioma is currently one of the hotspots of glioma research and may facilitate early intervention and efficacy assessment in glioma treatment, thereby improving glioma prognosis [9].

Long noncoding RNAs (lncRNAs) are a class of noncoding RNA molecules located in the nucleus or cytoplasm. According to statistics, there are approximately 58,000 lncRNAs in the human genome [10]. LncRNAs are divided into five categories: sense lncRNAs, antisense lncRNAs, bidirectional lncRNAs, intragenic lncRNAs, and intergenic lncRNAs [11]. They are closely associated with nervous system tumors [12]. LncRNAs are expressed in mature tissues or cells of the nervous system, such as embryonic stem cells, brain tissue [13], retina [14], and neural cell subtypes [15], and their expression levels vary across different types of neural cells [16]. Increasing evidence suggests that lncRNAs can act through multiple pathways and play important roles in glioma development by regulating DNA methylation [17], histone modification [18], and chromatin remodeling [19]. For example, LINC02587 can regulate its promoter sequence through methylation and induce ferroptosis in gliomas via the CoQ-FSP1 pathway [20]. LSD1 binds to the 3' domain of the lncRNA HOTAIR to specifically remove monomethylation and demethylation marks from H3K4 [21]. The lncRNA birc3-ot can guide the RELA protein to the STC1 promoter, initiate STC1 transcription, and ultimately promote the progression of glioma [17]. The H19 gene was one of the first identified lncRNAs involved in the pathogenesis of multiple CNS tumors [22]. Zhang et al. reported that lncRNA HOTAIR expression is closely related to the pathological grade and prognosis of glioma. Targeted silencing of HOTAIR inhibited the formation of glioma cell clones and tumor growth and induced the G0/G1 phase arrest of glioma cells [23]. The above studies indicate that lncRNAs play crucial roles in glioma. Recent studies have reported that LINC00601 expression is increased in HCC, and mechanistic studies have revealed that LINC00601 promotes HCC cell growth through the MAPK signaling pathway [24]. However, the role of LINC00601 in gliomas remains unknown.

The p-STAT3 signaling pathway plays an important role in gliomas. Elevated p-STAT3 activity is associated with increased proliferation, survival, and invasion of glioma cells, contributing to the aggressive nature [25]. Importantly, p-STAT3 has been identified as a promising therapeutic target. Inhibitors of this pathway have demonstrated potential in preclinical trials, showing reduced tumor growth and improved responses to conventional therapies [26]. These findings support the need for further exploration of p-STAT3 as both a prognostic marker and a therapeutic target in glioma treatment. However, the role of LINC00601 in gliomas has not been investigated, and its impact on the p-STAT3 signaling pathway also remains unclear.

In this study, bioinformatics analysis revealed that LINC00601 is highly expressed in glioma tissues and that this high expression is correlated with a poor prognosis in glioma patients. Further experiments revealed that LINC00601 affects the proliferation, migration, and invasion abilities of glioma cells in vitro and promotes tumor formation in vivo. Moreover, our study revealed a mechanism by which LINC00601 regulates p-STAT3 expression to promote the invasive growth of glioma. These results indicate that LINC00601 acts as a tumor-promoting factor in glioma and may be a potential novel therapeutic target for glioma diagnosis, treatment, and prognosis evaluation.

Bioinformatics analysis

Expression profiles and clinical sample data of glioma patients were downloaded from the China Glioma Genome Atlas (CGGA, www.CGGA.org) and the Cancer Genome Atlas (TCGA) databases.

Quantitative real-time PCR analysis

Total RNA was extracted from cultured glioma cell lines using TRIzol reagent (Invitrogen, Carlsbad, CA, USA). First-strand cDNA was synthesized from purified total RNA using the Thermoscript RT-PCR System (Takara) for first-strand cDNA synthesis. Briefly, each PCR reaction mixture, containing 10 ul of 2X SYBR-Green Master mix, 0.8 ul of sense and antisense primers (2.5 mM) and 5 ul of cDNA (10 ng), was run for 45 cycles with denaturation at 95°C for 15 seconds, annealing at 60°C for 30 seconds and extension at 72°C for 30 seconds. For relative quantification, 2^−ΔΔCT method was adopted to calculate the relative expression levels of LINC00601 and GAPDH by subtracting the CT values of the control gene from the CT values of LINC00601 and GAPDH. GAPDH mRNA were used as an internal control. The primers used were showed as follows: The primers used were showed as follows: GAPDH: F: 5’-GGGAGCCAAAAGGGTCAT − 3’ and R: 5’-GTCCTTCCACGATACCAA-3’. LINC00601: F: 5’- TCAAATGACCAACGGTCTGA − 3’ and R: 5’- GAGGAAGCTGTCTGGGTGAG-3’.

Cell culture procedures

Glioma U251 and U87 cells, and normal human astrocytes (HEB) were obtained from the American Type Culture Collection (ATCC; Manassas, VA, USA). Cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM), supplemented with 10% heat-inactivated fetal bovine serum (FBS) and 100 U/ml penicillin/streptomycin, at 37°C in a humidified atmosphere of 5% CO₂.

RNA interference (RNAi) analysis

In vitro, LINC00601 expression was disrupted to observe its functional effect on glioma cells. Glioma cell lines were first seeded in 6-well plates with serum-free medium and incubated overnight, then ,5 µL of sh-control, sh-LINC00601 vectors were diluted into 250 µL Opti-MEM (Invitrogen). Additionally, 5 µL of Lipofectamine 2000 (Invitrogen) was diluted into 250 µL Opti-MEM. Both mixtures were incubated at room temperature for 5 min. The Lipofectamine 2000 mixture was then added to the vector mixture. After 6 hours of incubation, the transfection solution was replaced with 2 mL of medium containing 10% FBS. Finally, transfected cells receiving the designed treatment were collected for further studies.

Cell proliferation

Cell proliferation was tested using CCK-8. Cells were harvested 48 hours after transfection, adjusted to a concentration of 3×10^4 cells/mL, and placed into 96-well plates. Each well was seeded with 100 µL of cells, and 10 µL of CCK-8 solution was put at 0, 24, 48, and 72 hours after cell adherence. After adding the reagent, the cells were incubated at 37°C with 5% CO2 for 2 hours, and then the optical density (OD) was measured at 450 nm to assess cell proliferation. This procedure was performed three times.

Cell migration assay and invasion assay

The invasive ability of the cells was assessed by the Transwell assay, A 4–7% Matrigel solution was mixed with medium without FBS, added to the Transwell upper chamber, and placed in a 37℃ incubator for solidification. Then, 200 uL of the cell suspension and 500 µL of DMEM or MEM containing 20% FBS were added to the Transwell upper and lower chambers, respectively. After incubation at 37℃ and 5% CO2 for 48 hours, the medium was aspirated with a pipette, and the cells in the upper chamber were wiped then rinsed in PBS for 5 minutes three times, fixed with 4% paraformaldehyde for 15 minutes, and rinsed in PBS for three times. Finally, the cells were stained with 0. 1% crystal violet for 10 minutes. Cellular invasion into the lower chamber was observed under a microscope. The experiment was repeated three times.

Tumor formation in nude mice

Four-week-old male BALB/c-nu athymic nude mice were housed in the animal room of the Animal Experiment Center at Anhui Medical University. They were randomly divided into two groups: a negative control group and an experimental group. The body weight of each nude mouse was recorded. U87 cells from both experimental and control groups were washed twice with PBS, digested with trypsin, collected, and counted. After discarding the supernatant, the cells were resuspended in pre-cooled PBS to a final concentration of 5×10^7 cells/mL. The cells were then placed on ice in preparation for the following experiments. Select the left armpit of the nude mice, disinfect with an alcohol swab, and prepare a 1 mL syringe sterilized by ultraviolet irradiation. Inject 120 µL of cell suspension slowly into the left armpit of the nude mice. Ensure not to inject into the chest cavity, as this is critical for the experimental procedure. Keep the cells on ice during the operation. Subcutaneous tumor growth in nude mice was observed daily. Tumor size was measured every 7 days using vernier calipers to measure the tumor length (L) and width (W). Tumor volume (mm^3) was estimated using the formula V = 0.5LW^2. Data were recorded and processed to depict the tumor growth curve. After 28 days, the two groups of nude mice were euthanized by CO2 inhalation (excluding accidental deaths). Tumors were photographed, weighed, and measured for size. Tumor volume was estimated, and tumors were either stored at -80°C or fixed in 4% paraformaldehyde for further analysis.

Statistical analysis

Quantitative data were obtained from at least three independent experiments and are expressed as mean ± SD. Data were analyzed for multiple comparisons using Student tests or ANOVA. The relationship between LINC00601 and p-STAT3 expression in tissues was analyzed using Pearson correlation. Values of p < 0.05 were considered to indicate a statistically significant difference. (*p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001)

Expression of LINC00601 in glioma tissues and its relationship with prognosis

To explore whether the upregulation of LINC00601 is related to the pathological grade of glioma, we analyzed the TCGA and CGGA databases; we found that significant upregulation of LINC00601 expression was associated with increased malignancy in glioma (Fig. 1A and 1B). Furthermore, LINC00601 expression was significantly upregulated in recurrent glioma tissues compared with primary glioma tissues (Fig. 1C and 1D). Moreover, high expression of LINC00601 was associated with a poor prognosis in glioma patients (Fig. 1E, 1F, and 1G). These results provide evidence that LINC00601 may be associated with glioma progression and prognosis.

In vitro inhibition of glioma cell growth by LINC00601 knockdown

To explore the functional roles of LINC00601, we transfected U251 and U87 human glioma cells with si-LINC00601 and verified the transfection efficiency via qRT‒PCR (Fig. 2A). Next, we established a negative control group (si-NC) and an experimental group (si-LINC00601) and assessed differences in malignant biological characteristics such as the proliferation, migration, and invasion of glioma cells between these groups. The impact of LINC00601 knockdown on the viability of U251 and U87 cells was assessed via the CCK-8 assay. The results indicated that, compared with the shRNA control, LINC00601 knockdown significantly reduced cell viability (Fig. 2B and 2C). A colony formation assay demonstrated that LINC00601 knockdown significantly inhibited colony formation in glioma cells. Transwell experiments revealed a significant reduction in the number of migratory U251 and U87 glioma cells in the LINC00601 knockdown group compared with that in the shRNA control group (Fig. 2D). Furthermore, LINC00601 knockdown significantly inhibited the invasion of U251 and U87 human glioma cells (Fig. 2E). These findings suggest that LINC00601 knockdown suppresses the malignant phenotype of glioma cells.

Bioinformatics analysis reveals an important relationship between LINC00601 and the p-STAT3 signaling pathway in gliomas

For the U87 glioma cell lines we constructed, 10 samples from both the si-LINC00601 and si-NC groups were selected for transcriptome analysis. We observed differences in gene expression in the transcriptome data between U87 glioma cells transfected with si-LINC00601 and those transfected with si-NC (Fig. 3A). These gene expression differences impact many biological processes, as demonstrated by GO enrichment analysis (Fig. 3B). Additionally, KEGG pathway enrichment analysis indicated that, in glioma, LINC00601 predominantly interacts with the JAK/STAT, NOD-like receptor, and TNF signaling pathways (Fig. 3C). We assessed the expression levels of STAT3 and p-STAT3 in both the control group and the si-LINC00601-treated U87 and U251 glioma cells via Western blot analysis (Fig. 3D and 3E) and confirmed that silencing LINC00601 significantly inhibited a key node of the JAK/STAT signaling pathway. Therefore, we hypothesized that LINC00601 influences glioma invasion by regulating the JAK/STAT signaling pathway.

p-STAT3 mediates the tumor-suppressive effects of LINC00601 knockdown in glioma cells

To investigate whether the tumor-promoting effects of LINC00601 are mediated by p-STAT3, U87 and U251 cells were transfected with Stattic (a potent STAT3 inhibitor that exerts its effects by inhibiting STAT3 phosphorylation at Y705 and S727), si-LINC00601, or si-LINC00601 + Stattic. Our results showed that Stattic can inhibit the proliferation of glioma cells and transfection with si-LINC00601 and combined with Stattic treatment enhances this inhibition. As shown here, Stattic increased the ability of si-LINC00601 to reduce the viability (Fig. 5A and 5B), proliferation (Fig. 5C and 5D), migration (Fig. 5E and 5F), and invasion (Fig. 5G and 5H) of U251 and U87 glioma cells. Therefore, these results suggest that LINC00601 may exert its oncogenic function in glioma cells through p-STAT3.

LINC00601 gene knockdown inhibits tumor formation in nude mice in vivo

U87 cells stably transfected with sh-NC or sh-LINC00601 were subcutaneously injected into the posterior flank of nude mice. The mice were euthanized and the tumor masses were removed 28 days after the injection. (B) Tumor volume was measured every 7 days via calipers. (A and C) The tumor tissues were excised and weighed. (D) The expression levels of LINC00601 in resected tumor tissues were determined via qRT‒PCR analysis. (E) H&E and Ki-67 staining of tumor tissues was performed.

To investigate the effect of the LINC00601 gene in vivo, we used a lentiviral transduction method to establish stable control vector short hairpin RNA (sh-NC) and short hairpin RNA LINC00601 (sh-LINC00601) U87 cell lines in both groups. Two groups of cells suspended in matrix glue were injected subcutaneously into the underarms of two groups of nude mice to initiate tumor formation experiments. qRT‒PCR was used to verify the silencing efficiency of LINC00601 in the experimental group (Fig. 5D). We evaluated tumor formation in nude mice. The results shown in the figure indicate that after LINC00601 expression was reduced, tumor size in nude mice was measured every 7 days. At 28 days, the tumor tissue was removed, and the results indicated that the tumors in the knockdown group were smaller than those in the experimental group (Fig. 5A). LINC00601 knockdown significantly suppressed tumor growth, as evidenced by the reduced tumor volume (Fig. 5B) and tumor weight (Fig. 5C). H&E and Ki-67 staining were subsequently performed on the tumor tissue and revealed significantly lower levels of staining in the knockdown group than in the control group (Fig. 5E). Thus, these results suggest that the inhibition of LINC00601 expression suppresses glioma cell growth in vivo.

Glioma is a type of tumor derived from glial cells in the spine or brain and accounts for approximately 80% of malignant brain tumors [27]. At present, the treatment of glioma primarily relies on surgery supplemented by postoperative radiotherapy and chemotherapy. Owing to their invasive growth characteristics, gliomas cannot be completely removed by surgery [28]. Therefore, identifying effective biomarkers for the early diagnosis of glioma can improve patient treatment outcomes and prognosis. Through bioinformatics analysis and biological experiments, this study revealed that LINC00601 acts as a potential prognostic marker and oncogene in glioma.

The LINC00601 gene, noted for its elevated expression in various cancers, is located on chromosome 10 at position 10q26.2. It spans 8,013 bases and is oriented on the minus strand. Y.-C. WANG et al. first demonstrated in vitro that LINC00601 promotes HCC cell proliferation, affects cell cycle distribution and inhibits apoptosis in the G1/G0 phase [24]. SHI X. et al. reported that LINC00601 expression may be associated with a poor prognosis in patients with esophageal squamous cell carcinoma [29]. In this study, we observed significant upregulation of LINC00601 in glioma, along with a strong correlation between its expression and histological grade. Elevated p-STAT3 activity has been associated with increased proliferation, survival, and invasion of glioma cells, contributing to the aggressive nature of these tumors [25]. Thus, LINC00601 may be related to the p-STAT3 signaling pathway, which needs to be confirmed by further study. Furthermore, our findings indicate that high LINC00601 expression is significantly associated with reduced overall survival and increased recurrence risk in glioma patients. Functionally, knockdown of LINC00601 significantly inhibited cell proliferation, colony formation, migration, and invasion in vitro and tumor growth in vivo. Overall, LINC00601 can be considered a potential prognostic marker and therapeutic target for gliomas.

LncRNAs are RNA molecules that are more than 200 nucleotides in length and cannot be translated into proteins due to the lack of a promoter [30]. Although lncRNAs do not directly participate in protein coding, an increasing number of experimental findings have demonstrated that their abnormal expression leads to tumor cell development, which subsequently impacts prognosis and survival rates. For example, H19 lncRNA expression is significantly increased in many human malignant tumors, and elevated H19 expression is typically associated with a poor prognosis in cancer patients [31]. Ohgaki H et al. investigated autophagy-related lncRNAs in glioma patients and identified 10 such lncRNAs as independent prognostic factors [32]. Five of these lncRNAs (TP53TG1, ZNF674-AS1, COX10AS1, DDX11-AS1, and SBF2-AS1) were identified as adverse prognostic factors, whereas the other five (PCBP1)-AS1, DHRS4-AS1, GABPB1-AS1, MAPKAPK5-AS1, and MIR4453HG) were favorable prognostic factors [33]. In this study, using the TCGA and CGGA databases, we found that upregulation of LINC00601 expression is associated with increased malignancy and a poor prognosis in glioma patients. Additionally, LINC00601 expression was significantly higher in recurrent gliomas than in primary gliomas. These findings suggest that LINC00601 could serve as a potential prognostic marker and therapeutic target for glioma.

LncRNAs play crucial roles in regulating cell proliferation, apoptosis, differentiation, and the response to hypoxia stress by actively participating in nuclear interference [34], transcriptional activation [35], and chromatin modification [28]. Consequently, they play key roles in the progression of glioma.

Zhou, K et al. reported that the expression of the lncRNA NEAT1 is upregulated in glioma. It promotes glioma formation by inhibiting the expression of miR-132, thereby alleviating the negative regulatory effect of miR-132 on SOX2 [36]. In primary GBM tumors, SChLAP1 expressed at high levels interacts with heterogeneous nuclear ribonucleoprotein L (HNRNPL), leading to increased binding of HNRNPL to α-actinin-4 (ACTN4). This interaction inhibits the degradation of ACTN4, which in turn increases the activity of nuclear factor κB (NF-κB) signaling, a pathway associated with cancer progression [37]. Here, we observed that the knockdown of LINC00601 suppressed the proliferation, migration, and invasion of glioma cells. Furthermore, knockdown of LINC00601 significantly inhibited glioma tumor growth in vivo. These findings suggest that LINC00601 plays a cancer-promoting role both in vitro and in vivo.

As previously discussed, the expression of lncRNAs in gliomas differs significantly from that in normal tissues. Research has confirmed that lncRNAs are involved in various signaling pathways, influencing the proliferation, migration, invasion, and other behaviors of glioma cells, as well as the regulation of the tumor microenvironment. Consequently, lncRNAs may serve as therapeutic targets by modulating these pathways. The expression of the lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) is highly upregulated in glioma tissues. This RNA promotes cell proliferation, colony formation, migration, and invasion by activating the Wnt/β-catenin signaling pathway [38]. LINC01410 activates the Notch signaling pathway and accelerates glioma progression by sponging miR-506-3p and upregulating the NOTCH2 receptor [39]. The roles of lncRNAs in glioma mechanisms vary, and their underlying mechanisms have not yet been fully elucidated, so further in-depth studies are needed. In our study, by analyzing transcriptome data for normal U87 cells and U87 cells with LINC00601 knockdown, we discovered that LINC00601 primarily influences the JAK/STAT, NOD-like receptor, and TNF signaling pathways, along with associated biological behaviors. Our Western blot analysis also revealed that LINC00601 knockdown significantly inhibited a key node of the JAK/STAT signaling pathway. Therefore, we hypothesized that LINC00601 modulates glioma biological behavior by regulating the p-STAT3 signaling pathway. We discovered that Stattic alone can suppress the proliferation of glioma cells and that the combined application of si-LINC00601 and Stattic enhances this inhibitory effect. These findings confirmed that LINC00601 promotes glioma cell proliferation and invasion via the p-STAT3 signaling pathway.

In summary, our study revealed that LINC00601 is abnormally upregulated in gliomas and may serve as a valuable prognostic marker for glioma patients. LINC00601 plays a crucial role in glioma regulation by modulating the p-STAT3 pathway, thereby providing a new theoretical basis for glioma treatment.

lncRNAs	long non-coding RNAs
siRNA	small interfering RNA
shRNA	short hairpin RNA
qRT-PCR	quantitative real-time PCR
si-NC	control vector siRNA
si-LINC00601	siRNA LINC00601
p-STAT3	Transducer and Activator of Transcription 3

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

All experiments were in agreement with the guidelines for the Care and Use of Laboratory Animals and were approved by the Ethics and Welfare Committee for Animal Research at the Second Affiliated Hospital of Anhui Medical University.

Funding

This work was supported by the Research Project Fund of Natural Science from Anhui Medical University, China (Grant No. KJ2021A0326).

Author Contribution

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Chao Ma, Linqi WANG and Renwu Zhang . The first draft of the manuscript was written by Renwu Zhang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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No competing interests reported.

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LINC00601 promotes the progression of glioma via the p-STAT3 signaling pathway

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Background

Materials and Methods

Bioinformatics analysis

Quantitative real-time PCR analysis

Cell culture procedures

RNA interference (RNAi) analysis

Cell proliferation

Cell migration assay and invasion assay

Tumor formation in nude mice

Statistical analysis

Results

Expression of LINC00601 in glioma tissues and its relationship with prognosis

In vitro inhibition of glioma cell growth by LINC00601 knockdown

Bioinformatics analysis reveals an important relationship between LINC00601 and the p-STAT3 signaling pathway in gliomas

p-STAT3 mediates the tumor-suppressive effects of LINC00601 knockdown in glioma cells

LINC00601 gene knockdown inhibits tumor formation in nude mice in vivo

Discussion

Abbreviations

Declarations

Competing Interests

Ethics approval

Funding

Author Contribution

Data Availability

References

Additional Declarations

Status:

Version 1