SOX-17 is involved in invasion and apoptosis of colorectal cancer cells through regulating miR-302b-3p expression

The prognosis of advanced colorectal cancer (CRC) is currently still very poor, which suggests that the biological mechanisms of CRC oncogenesis are not fully understood. This study was conducted to explore the regulatory effect of SOX-17 on the expression of microRNA (miR)-302b-3p, and the involvement of SOX-17 in the invasion and apoptosis of CRC cells. The expression of SOX-17 and miR-302a,b,c,d-3p in colorectal cancer and normal colon epithelial cell lines was measured by real-time polymerase chain reaction and/or western blot. The regulatory effects of SOX-17 on miR-302b-3p gene in HT29 and LoVo cells were tested using the ChiP assay. The biological activities of SOX-17 and miR-302b-3p were evaluated by invasion and apoptosis assay. Results showed that transfection of SOX-17 small interfering RNA (siSOX-17) significantly increased, whereas transfection of SOX-17 overexpression vector (oeSOX-17) significantly decreased, miR-302b expression in HT29 and LoVo cells. Cotransfection of oeSOX-17 and miR-302b-3p inhibitor (INmiR-302b) significantly blocked the effects of SOX-17 in HT29 and LoVo cells. ChIP experiments showed that SOX-17 bonded to the miR-302b-3p promoter in HT29 and LoVo cells. Transfection of oeSOX-17 and miR-302b-3p mimics (MImiR-302b) significantly decreased, whereas transfection of siSOX-17 and INmiR-302b significantly increased, the invasion of HT29 and LoVo cells. In contrast, transfection of oeSOX-17 and MImiR-302b significantly increased, while transfection of siSOX-17 and INmiR-302b significantly decreased, apoptosis in HT29 and LoVo cells. Cotransfection of oeSOX-17 and INmiR-302b significantly blocked the effects of oeSOX-17 on cell invasion and apoptosis in HT29 and LoVo cells. These results suggested that SOX-17 can bind to the promoter of miR-302b-3p gene to regulate its expression, while both SOX-17 and miR-302b regulate the invasion and apoptosis in colorectal cancer cells.     

Circular RNA circ_0074026 indicates unfavorable prognosis for patients with glioma and facilitates oncogenesis of tumor cells by targeting miR-1304 to modulate ERBB4 expression

Glioma (GM) is a common malignancy all over the world. A novel circular RNA (circRNA), circ_0074026, has been documented to be upregulated in GM tissues than that of normal counterparts, as confirmed by circRNA microarray. However, the biological mechanism of circ_0074026 is still unreported in GM. The expression of circ_0074026 in GM specimens or cells was detected by quantitative real-time polymerase chain reaction. Fisher's exact test was utilized to evaluate the clinical relevance of circ_0074026 in patients with GM. Kaplan–Meier and Cox regression analysis were used to estimate the prognostic value of circ_0074026. Cell counting kit-8 (CCK-8), acridine orange/ethidium bromide double fluorescence staining, flow cytometry, wound healing, and Transwell assays were used to detect the malignant behaviors of GM cells including cell growth, apoptosis, migration, and invasion. CCK-8 and flow cytometric experiments were utilized to evaluate whether circ_0074026 had a side effect on normal human astrocyte cells. The interaction between miR-1304 and circ_0074026 or ERBB4 3′-untranslated region (3′-UTR) was predicted with circular RNA Interactome and TargetScan, respectively, and then confirmed by the dual-luciferase reporter test. The levels of circ_0074026 were both apparently increased in GM samples and cells. The elevated expression of circ_0074026 was linked to patients’ tumor size, WHO grade, disease-free survival, and overall survival. The depletion of circ_0074026 can block cell growth, migration, invasion, and impel cell apoptosis in the LN229 cell line. However, ectopically expressed circ_0074026 caused the opposite effect in the U251 cell line. The following dual-luciferase reporter assay demonstrated that miR-1304 interacted with circ_0074026 and ERBB4 3′-UTR. Furthermore, the rescue assay indicated that circ_0074026 modulated ERBB4 to promote tumor progression by regulating miR-1304. Thus, a novel regulatory pathway may provide a new therapeutic target for patients with GM.     

LncRNA SNHG12 promotes proliferation and epithelial mesenchymal transition in hepatocellular carcinoma through targeting HEG1 via miR-516a-5p

Hepatocellular carcinoma (HCC) is the most common cancer and its prognosis is poor due to metastasis and recurrence. EMT is associated with metastasis. A deep understanding of regulatory mechanism of EMT is critical. LncRNA is involved in regulation of various biological processes including EMT. This study aimed to investigate the regulatory signal axis among lncRNA SNHG12, miR-516a-5p and the target gene HEG1 during EMT. Cell cycle and apoptosis were analyzed by flow cytometry. Tumorigenesis was analyzed by clone formation assay. Wound healing assay and transwell assay was performed to detect migration and invasion, respectively. Interaction among SNHG12, miR-516a-5p and HEG1 were analyzed by dual luciferase assay and RIP assay. We also detected expression of RNA and protein by QPCR and western blotting. Finally, tumor growth was analyzed by tumorigenesis assay in vivo. Ki-67 and HEG1 level in tumor tissues was analyzed by IHC. SNHG12 and HEG1 were upregulated, miR-516a-5p was downregulated in HCC cell lines. SNHG12 could interact with and inhibit miR-516a-5p. MiR-516a-5p could interact with HEG1 and inhibit HEG1 expression. Knock down SNHG12 inhibited proliferation, migration, invasion, EMT and promoted apoptosis of HCC cells. Such effects were antagonized by inhibiting miR-516a-5p. SNHG12 overexpression lead to opposite results. Similar results were observed in mice. SNHG12 could promote EMT in HCC through targeting and inhibiting miR-516a-5p, which eventually upregulated HEG1 expression, in both cell and mice.     

Overexpression of circ_0005198 sponges miR-1294 to regulate cell proliferation,apoptosis, migration,and invasion in glioma

Glioma (GM) is an aggressive malignancy with high mortality rate across the world. Mounting studies demonstrates that abnormally expressed circular RNAs (circRNAs) act as important roles in tumor progression. In the current work, a novel circRNA, circ_0005198, was explored. Circ_0005198 level in GM tissue samples and cells was detected. The clinical implication of circ_0005198 was analyzed by Fisher's test and Kaplan-Meier analysis. In vitro experiments were carried out to elucidate the influence of circ_0005198 on GM cell proliferation, apoptosis, and metastatic properties. Luciferase reporter and rescue experiments were conducted to clear the mechanism of circ_0005198. The expression of circ_0005198 was enhanced in GM tumors and cells. Its expression in tumor specimens was related to clinical severity and poor prognosis. Functionally, circ_0005198 could remarkably boost cell growth, clone-forming ability, and metastatic properties and attenuate cell apoptosis in GM cells. What's more, circ_0005198 could directly sponge miR-1294 to exert oncogenic functions. In summary, this study might provide an effective therapeutic target for GM.     

CRKL promotes cell proliferation in gastric cancer and is negatively regulated by miR-126

V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family and act as an adaptor protein participating in intra-cellular signal transduction. The role of CRKL in gastric cancer (GC) remains unclear. In this study, we show that CRKL was aberrantly highly expressed in both GC tumor specimens and cell lines (SGC-7901, MKN-45, MKN-28 and SUN-16). The expression of CRKL was significantly correlated with GC clinicopathologic features including tumor size, local invasion, lymph node metastasis and TNM stages. Knock-down of CRKL in SGC-7901 cells induced a suppression of cell proliferation along with a significant arrest of cell cycle in G0/G1 phase, however, no significant influence was observed on cell apoptosis. We validate that miR-126, a suppressor in GC, was a negative regulator of CRKL by directly combining with the 3′ untranslated region of CRKL mRNA, and over-expression of miR-126 inhibited the protein expression of CRKL significantly. These results suggest that CRKL may function as an oncogene in GC by promoting the GC cell proliferation, which provides us a likely biomarker and a potential target for GC prevention, diagnosis and therapeutic treatment. Moreover, the targeting relationship between CRKL and miR-126 partly reveals the mechanism of miR-126 on GC suppression.     

miR-135b promotes proliferation and metastasis by targeting APC in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The aim of our study was to investigate the functional role of microRNA-135b (miR-135b) in TNBC. A real-time polymerase chain reaction assay was used to quantify miR-135b expression levels in 90 paired TNBC tissue and adjacent normal tissue samples. Wound-healing and transwell assays were performed to evaluate the effects of miR-135b expression on the migration and invasion of TNBC cells. Luciferase reporter and western blot analyses were used to verify whether the mRNA encoding APC is a major target of miR-135b. In the current study, we found that miR-135b was highly expressed in TNBC tissue and cells, and the expression levels were correlated with lymph node status and TNM stage. In TNBC cells, the ectopic expression of miR-135b promoted cell proliferation and invasion in vitro. In addition, our study proved that the overexpression of miR-135b significantly suppressed APC expression by targeting the 3′-untranslated region of APC, whereas enhanced APC expression could partially abrogate the miR-135b-mediated promotion of carcinogenic traits in TNBC cells. Taken together, our study demonstrated that miR-135b expression promoted the proliferation and invasion of TNBC by downregulating APC expression, indicating that miR-135b may serve as a promising target for the treatment of TNBC patients.     

miR-30a和miR-30b靶向GW182的生物学功能研究

目的：通过证明miR-30a、miR-30b靶向GW182,探索HeLa细胞中miR-30a、miR-30b及GW182的生物学功能。方法：生物信息学预测分析表明GW182的3＇UTR区存在4个保守的miR-30a、miR-30b靶位点,将含有靶位点的序列片段构建到萤光素酶报告载体中,检测miR-30a、miR-30b与靶位点的结合情况;用阳离子脂质体转染GW182 siRNA和miR-30a、miR-30b mimics,检测GW182下游功能的变化。结果：miR-30a、miR-30b能够靶向GW182;qPCR及Western印迹证明miR-30a、miR-30b可以在mRNA与蛋白水平上降低GW182的表达,同时影响GW182所参与的miRNA/siRNA对靶基因的抑制作用。结论：GW182是miR-30a、miR-30b的靶基因,揭示了miR-30a、miR-30b通过靶向GW182影响miRNA/siRNA作用途径的新功能。     

Circ_0079593 facilitates proliferation,metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR-516b/GRM3 axis

Many studies confirm that circular RNA (circRNA) plays an important regulatory role in the malignant progression of cancer, including melanoma. However, the role of a novel circRNA, circ_0079593, in melanoma is unclear. The expression levels of circ_0079593 and miR-516b were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was measured by cell counting kit-8 (CCK-8) assay, and cell migration and invasion were evaluated using transwell assay. Meanwhile, western blot (WB) analysis was employed to determine the levels of proliferation and metastasis-related proteins, as well as metabotropic glutamate receptor 3 (GRM3) protein. Furthermore, cell apoptosis was tested by detecting the cell apoptosis rate and Caspase-3 activity. The glucose consumption and lactate production of cells were measured to evaluate cell glucose metabolism. Moreover, dual-luciferase reporter assay and biotin-labeled RNA pull-down assay were used to confirm the interaction between miR-516b and circ_0079593 or GRM3. In addition, mice xenograft models were constructed to explore the effect of circ_0079593 on melanoma tumor growth in vivo. Our results discovered that circ_0079593 was highly expressed in melanoma, and its silencing suppressed melanoma cell proliferation, migration, invasion, glucose metabolism and promoted apoptosis. Moreover, we found that circ_0079593 could serve as a sponge of miR-516b, and miR-516b could target GRM3 in melanoma. The rescue experiments revealed that both miR-516b inhibitor and GRM3 overexpression could reverse the inhibition effect of circ_0079593 knockdown on melanoma progression. Additionally, in vivo experiments also revealed that circ_0079593 interference suppressed melanoma tumor growth. Our study concluded that circ_0079593 accelerated melanoma progression via upregulating GRM3 by sponging miR-516b, which suggested that circ_0079593 had the potential to be a new therapeutic biomarker for melanoma.

     

Long noncoding RNA PTENP1 affects the recovery of spinal cord injury by regulating the expression of miR-19b and miR-21

Exosomes derived from differentiated P12 cells and MSCs were proved to suppress apoptosis of neuron cells, and phosphatase and tensin homolog pseudogene 1 (PTENP1) was reported to inhibit cell proliferation. In this study, we aimed to investigate the role of PTENP1 in the process of post-spinal cord injury (SCI) recovery, so as to evaluate the therapeutic effects of exosomes derived from MSCs transfected with PTENP1 short hairpin RNA (shRNA), as a type of novel biomarkers in the treatment of SCI. Electron microscopy was used to observe the morphology of different exosomes. Real-time polymerase chain reaction and western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry, Nissl staining, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were conducted to investigate and validate the underlying molecular signaling pathway. PTENP1-shRNA downregulated PTENP1 and PTEN while upregulating miR-21 and miR-19b. PTENP1-shRNA also accelerated cell apoptosis and reduced cell viability. In addition, PTENP1 reduced the miR-21 and miR-19b expression by directly targeting miR-21 and miR-19b. Meanwhile, both miR-21 and miR-19b reduced the expression of PTEN by directly targeting the 3′-untranslated region of PTEN. Furthermore, PTEN level and apoptosis index of neuron cells was the highest in the SCI group, while the treatment with exosomes+PTENP1-shRNA reduced the PTEN expression to a level similar to that in the sham group. Finally, PTENP1 inhibited miR-21 and miR-19b expression but upregulated PTEN expression. The upregulation of miR-21/miR-19b also suppressed the apoptosis of neuron cells by downregulating the PTEN expression. PTENP1 is involved in the recovery of SCI by regulating the expression of miR-19b and miR-21, and exosomes from PTENP1-shRNA-transfected cells may be used as a novel biomarker in SCI treatment.     

LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging

LBX2-AS1 is a long non-coding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated. Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti-cancer treatment in our facility were analysed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumour formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral-based LBX2-AS1 knockdown. ENCORI platform was used to explore LBX2-AS1-interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA pulldown assay were used to verify the putative miRNA-RNA interactions. Ovarian cancer tissue specimens showed significant higher LBX2-AS1 expression levels that non-cancerous counterparts. High expression level of LBX2-AS1 was significantly associated with reduced overall survival of patients. LBX2-AS1 knockdown significantly down-regulated the cell growth, colony formation, migration, invasion and tumour formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2-AS1 interacts with and thus inhibits the function of miR-455-5p and miR-491-5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2-AS1 knockdown on ovarian cancer cells. LBX2-AS1 was a novel cancer-promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumour formation of ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, thus liberating the expression of E2F2 cancer-promoting gene.     

Differential expression of miR-195 in esophageal squamous cell carcinoma and miR-195 expression inhibits tumor cell proliferation and invasion by targeting of Cdc42

MicroRNAs (miRNA) have played an important role in carcinogenesis. In this study, Agilent miRNA microarray was used to identify differentially expressed miRNAs in esophageal squamous cell carcinoma (ESCC) tissues and miR-195 was downregulated in ESCC compared with normal esophageal tissues. Moreover, Cdc42 was confirmed as target gene of miR-195. Ectopic expression of miR-195 in ESCC cells significantly downregulated Cdc42 by directly binding its 3′ untranslated regions, and induced G1 cell cycle arrest, leading to a significant decrease in cell growth, migration, and invasion in vitro. Therefore, our findings demonstrated that miR-195 may act as a tumor suppressor in ESCC by targeting Cdc42.     

miR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2

Mounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR-144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR-144 and LIM homeobox 2 (LHX2) expression in CDDP-resistant and the parental cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. The functions of miR-144 overexpression on cell viability, the incidence of apoptosis, the activity of caspase-3/7, the cleaved-caspase-3 expression, cell migration, and invasion were determined in Hela cells and Hela/CDDP cells. Overexpression of miR-144 reduced cell viability, induced cell apoptosis, and inhibited cell migration and invasion after CDDP treatment. Besides, a luciferase reporter system demonstrated that miR-144 could directly bind to the 3′ untranslated region (3′-UTR) of LHX2 messenger RNA (mRNA). Gain expression of miR-144 decreased the expression of LHX2 both in mRNA and protein levels. Furthermore, restoration of LHX2 partly abolished the biological functions of miR-144 in resistance of cervical cancer cells. Taken together, miR-144 overcomes resistance to CDDP via promoting cell apoptosis and inhibiting invasion through targeting LHX2 in cervical cancer cells.     

LncRNA GACAT1 induces tongue squamous cell carcinoma migration and proliferation via miR-149

Recent studies have observed that lncRNAs (long non-coding RNAs) are involved in the progression of various tumours including tongue squamous cell carcinoma (TSCC). Recently, a new lnRNA, GACAT1, has been firstly identified in gastric cancer. However, its potential role in TSCC remains unknown. In this reference, we observed that GACAT1 was overexpressed in TSCC samples and cell lines. Of 25 TSCC specimens, GACAT1 expression was overexpressed in 18 patients (18/25, 72%) compared to non-tumour specimens. Ectopic expression of GACAT1 induced cell growth and migration and promoted epithelial to mesenchymal transition in TSCC. In addition, ectopic expression of GACAT1 decreased miR-149 expression in SCC1 cell. We observed that miR-149 expression was down-regulated in TSCC cell lines. Moreover, we observed that GACAT1 expression was negatively correlated with miR-149 expression. GACAT1 overexpression induced TSCC cell growth and migration via regulating miR-149 expression. These data provided that GACAT1 played an oncogenic role in the progression of TSCC partly through modulating miR-149 expression.     

Circular RNA circ_0079593 indicates a poor prognosis and facilitates cell growth and invasion by sponging miR-182 and miR-433 in glioma

Glioma is one of the major global health problems, including in China. Circular RNAs (circRNAs) have been increasingly identified and characterized in almost every aspect of biology, especially in cancer biology. This research desires to explore the functions and mechanism of a novel circRNA, circ_0079593, on regulating glioma progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to measure the relative expression of circ_0079593, which was upregulated in matched cancerous tissues from 60 patients and four cell lines of glioma. A higher level of circ_0079593 in glioma specimens was linked to larger tumor size, higher WHO grade, and worse survival rate for patients with glioma. Moreover, circ_0079593 can be deemed as an independent prognostic predictor for glioma patients analyzed by multivariate method. Cell counting kit-8, flow cytometric, wound healing, and transwell experiments were used to evaluate cell growth, apoptosis, migration, and invasion influenced by circ_0079593 knockdown/overexpression. Exogenous downregulation of circ_0079593 expression significantly suppressed glioma cell proliferation by increasing cell apoptosis in vitro, and retarded the migratory and invasive potential. Ectopic expressed circ_0079593 could induce the opposite effects. Mechanistically, bioinformatics analysis, qRT-PCR, and dual-luciferase reporter assays showed that microRNA 182 (miR-182) and miR-433 could be sponged and negatively regulated by circ_0079593. Further, rescue assays demonstrated that the biological functions of circ_0079593 are dependent on its inhibition of miR-182 and miR-433. Collectively, the present work indicates that circ_0079593 may be used as an effective prognostic marker and therapeutic target for glioma.     

Long noncoding RNA ABHD11-AS1 promote cells proliferation and invasion of colorectal cancer via regulating the miR-1254-WNT11 pathway

The purpose of our study was to investigate the effects of the long noncoding RNA (lncRNA) ABHD11-AS1 on colorectal cancer (CRC) progression and further explore its possible underlying mechanisms. In the study, we found that ABHD11-AS1 was highly expressed in CRC tissues and cell lines. High ABHD11-AS1 expression was correlated with poor overall survival of patients with CRC. ABHD11-AS1 knockdown reduced CRC cell proliferation, in vitro invasion, and in vivo tumor growth. Investigation of the underlying mechanism showed that ABHD11-AS1 could act as a molecular sponge of miR-1254, and WNT11 was a downstream target of miR-1254 in CRC. Moreover, there was a negative association between ABHD11-AS1 expression (or WNT11) and miR-1254 in CRC tissues. The rescue assays showed that WNT11 overexpression partially rescued the effects of ABHD11-AS1 inhibition on CRC progression. Thus, we demonstrated that ABHD11-AS1 promotes CRC progression through the miR-1254-WNT11 pathway, which provides a new insight into the therapeutic strategies for CRC.     

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

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

miR-19a and miR-424 target TGFBR3 to promote epithelial-to-mesenchymal transition and migration of tongue squamous cell carcinoma cells

Previous studies indicate that TGFBR3 (transforming growth factor type III receptor, also known as betaglycan), a novel suppressor of progression in certain cancers, is down-regulated in tongue squamous cell carcinoma (TSCC). However, the role of this factor as an upstream regulator in TSCC cells remains to be elucidated. The present study was designed to elucidate whether TGFBR3 gene expression is regulated by two microRNA molecules, miR-19a and miR-424. The study also aimed to determine if these microRNAs promote migration of CAL-27 human oral squamous cells. Immunohistochemistry (IHC) and western blot analyses demonstrated that TGFBR3 protein levels were dramatically down-regulated in clinical TSCC specimens. Conversely, bioinformatics analyses and qRT-PCR results confirmed that both miR-19a and miR-424 were markedly up-regulated in clinical TSCC specimens. In this study, we observed that transfection of a TGFBR3-containing plasmid dramatically inhibited epithelial-to-mesenchymal transition (EMT) and migration in CAL-27 cells. Co-immunoprecipitation analyses also revealed that TGFBR3 forms a complex with the β-arrestin 2 scaffolding protein and IκBα. Furthermore, overexpression of TGFBR3 decreased p-p65 expression and increased IκBα expression; these effects were subsequently abolished following knockdown of β-arrestin 2. Moreover, over-expression of miR-19a and miR-424 promoted migration and EMT in CAL-27 cells. We also observed that the promotion of EMT by miR-19a and miR-424 was mediated by the inhibition of TGFBR3. Our study provides evidence that miR-19a and miR-424 play important roles in the development of TSCC. These results expand our understanding of TGFBR3 gene expression and regulatory mechanisms pertaining to miRNAs.