HOXA Transcript At The Distal Tip Overexpression Research Articles

M1 macrophage-derived exosomes and their key molecule lncRNA HOTTIP suppress head and neck squamous cell carcinoma progression by upregulating the TLR5/NF-\u03baB pathway

Exosomes serve as a crucial mode of communication between tumor-associated macrophages (TAMs) and cancer cells. This study attempted to explore the function of M1-derived exosomes and clarify their specific mechanism in head and neck squamous cell carcinoma (HNSCC). Moreover, the functional roles of M1-derived exosomes and their key molecule long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) in HNSCC were investigated by conducting a series of in vitro and in vivo experiments. The dual-luciferase test was utilized to clarify the binding capacities between HOTTIP/mRNA and miRNAs. Accordingly, HOTTIP was found to be upregulated in M1-derived exosomes. Meanwhile, the in vitro experiments indicated that M1 exosomes suppressed proliferation, migration and invasion but induced apoptosis of cancer cells. This function was noted to be enhanced by HOTTIP-overexpressed M1 exosomes but was weakened by HOTTIP-knockdown ones, indicating that HOTTIP serves as a key molecule in M1 exosomes. Therefore, the function of HOTTIP in cancer cells was explored, for which overexpression of HOTTIP was found to inhibit proliferation, migration and invasion but induced apoptosis of cancer cells in vitro. A mechanism study further showed that M1 exosomes and HOTTIP activated the TLR5/NF-κB signaling pathway by competitively sponging miR-19a-3p and miR-19b-3p. Furthermore, cancer cells expressing HOTTIP were noted to induce the polarization of both local M1 and M2 macrophages; however, M1 exosomes were observed to reprogram local TAMs into M1 macrophages. More importantly, both cancer cells expressing HOTTIP and M1 exosomes reeducated circulating monocytes to express the M1 phenotype. The corresponding data demonstrated that the M1 exosomal lncRNA HOTTIP suppresses HNSCC progression by upregulating the TLR5/NF-κB signaling pathway through competitively sponging miR-19a-3p and miR-19b-3p. In particular, M1 exosomes and HOTTIP induce the polarization of M1 in circulating monocytes, thus providing novel insight into HNSCC immunotherapy.

LncRNA HOTTIP PROMOTES OVARIAN CANCER CELL INVASION AND METASTASIS BY STABILIZING HIF-1α IN THE ANOXIC CELLULAR MICROENVIRONMENT.

The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF-1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

Long noncoding RNA HOTTIP promotes the metastatic potential of ovarian cancer through the regulation of the miR-615-3p/SMARCE1 pathway.

Upregulation of lncRNA HOXA transcript at the distal tip (HOTTIP) plays important roles in cancer progression. Nevertheless, its functions in the growth and metastasis of ovarian carcinoma are unknown. In this study, we demonstrated overexpression of HOTTIP in ovarian cancer cell lines and clinical tissues. Further, we showed that higher level of HOTTIP was associated with poor survival of ovarian cancer patients. Notably, HOTTIP silencing restrained proliferation, migration, and invasiveness of ovarian carcinoma cells. On the other hand, upregulation of HOTTIP remarkably exacerbated the aggressive traits of ovarian carcinoma cells. In addition, HOTTIP served as a sponge of miR-615-3p to upregulate SMARCE1 level. Further, upregulation of miR-615-3p or downregulation of SMARCE1 reversed the carcinogenic impacts of HOTTIP in ovarian cancer. HOTTIP and miR-615-3p expression levels in ovarian cancer cells were negatively correlated, whereas HOTTIP and SMARCE1 expression levels were positively correlated. In nude mice, downregulation of HOTTIP reduced cell growth in vivo. In summary, lncRNA HOTTIP promotes the growth and metastatic phenotypes of ovarian cancer via regulating miR-615-3p/SMARCE1 pathway.

LncRNA HOTTIP facilitates the stemness of breast cancer via regulation of miR-148a-3p/WNT1 pathway.

Emerging evidence suggests that dysregulation of long non‐coding RNA (lncRNA) plays a key role in tumorigenesis. The lncRNA, HOXA transcript at the distal tip (HOTTIP), has been reported to be up‐regulated in multiple cancers, including breast cancer, and is involved in various biological processes, including the maintenance of stemness. However, the biological function and underlying modulatory mechanism of HOTTIP in breast cancer stem cells (BCSCs) remains unknown. In this study, we found that HOTTIP was markedly up‐regulated in BCSCs and had a positive correlation with breast cancer progression. Functional studies revealed that overexpression of HOTTIP markedly promoted cell clonogenicity, increased the expression of the stem cell markers, OCT4 and SOX2, and decreased the expression of the differentiation markers, CK14 and CK18, in breast cancer cells. Knockdown of HOTTIP inhibited the CSC‐like properties of BCSCs. Consistently, depletion of HOTTIP suppressed tumour growth in a humanized model of breast cancer. Mechanistic studies demonstrated that HOTTIP directly binds to miR‐148a‐3p and inhibits the mediation of WNT1, which leads to inactivation of the Wnt/β‐catenin signalling pathway. Our study is the first to report that HOTTIP regulates the CSC‐like properties of BCSCs by as a molecular sponge for miR‐148a‐3p to increase WNT1 expression, offering a new target for breast cancer therapy.

HOTTIP knockdown inhibits cell proliferation and migration via regulating miR-490-3p/HMGB1 axis and PI3K-AKT signaling pathway in ox-LDL-induced VSMCs

AimsAtherosclerosis (AS) is a common cardiovascular disease with complicated pathogenesis. Long non-coding RNAs (lncRNAs) have been reported to be associated with AS progression. We aimed to explore the role and underlying mechanism of HOXA transcript at the distal tip (HOTTIP) in AS. Materials and methodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HOTTIP, miR-490-3p and high mobility group B 1 (HMGB1) in AS patients' sera and oxidized low-density lipoprotein (ox-LDL) induced human aortic vascular smooth muscle cells (HA-VSMCs). Cell Counting Kit-8 (CCK-8) assay and transwell assay were conducted to evaluate the proliferation and migration of HA-VSMCs, respectively. Western blot assay was carried out to determine the levels of proliferating cell nuclear antigen (PCNA), matrix metalloprotein 2 (MMP2), MMP9 and HMGB1. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the targeting association between HOTTIP and miR-490-3p, as well as miR-490-3p and HMGB1. Key findingsHOTTIP and HMGB1 were upregulated and miR-490-3p was downregulated in the sera of AS patients and ox-LDL-stimulated HA-VSMCs. HOTTIP knockdown suppressed ox-LDL induced proliferation and migration in HA-VSMCs. MiR-490-3p was identified as a target of HOTTIP and HOTTIP overexpression abolished the inhibition on cell proliferation and migration mediated by miR-490-3p in ox-LDL-induced HA-VSMCs. Moreover, miR-490-3p inhibition promoted cell proliferation and migration by directly targeting HMGB1 in ox-LDL-induced HA-VSMCs. Besides, HOTTIP knockdown repressed the activation of PI3K-AKT signaling pathway. SignificanceHOTTIP knockdown suppressed cell proliferation and migration by regulating miR-490-3p/HMGB1 axis and PI3K-AKT pathway in ox-LDL-induced HA-VSMCs.

LncRNA HOTTIP enhances human osteogenic BMSCs differentiation via interaction with WDR5 and activation of Wnt/β-catenin signalling pathway

To uncover the underlying molecular mechanism of long non-coding RNA in the osteogenic differentiation process of bone marrow mesenchymal stem cells (BMSCs), HOXA transcript at the distal tip (HOTTIP) was selected by using a lncRNA microarray assay. Results showed that HOTTIP was significantly upregulated during osteogenic differentiation of human BMSCs. Downregulation of HOTTIP by shRNA inhibited the osteogenic differentiation of BMSCs. Overexpression of HOTTIP by lentiviral vector promoted human BMSCs osteogenic differentiation by increasing the transcription of β-catenin. RIP assay and RNA pulldown assay confirmed the interaction between HOTTIP and WDR5, a transcription factor binding to the promoter of β-catenin. The interaction promoted the translocation of WDR5 into the nucleus and increased the transcription of β-catenin. Implanted HOTTIP-overexpressing BMSCs increased ectopic bone formation in nude mice. HOTTIP is a conservative long noncoding RNA that is essential for osteogenic differentiation of BMSC. HOTTIP enhances osteogenic differentiation via interaction with WDR5 and up-regulation of β-catenin gene expression, therefore activating Wnt/β-catenin signalling pathway.

Long non-coding (lnc)RNA PAPAS overexpression inhibits tumor growth in papillary thyroid carcinoma by downregulating lncRNA HOTTIP.

The long non-coding (lnc)RNA pre-ribosomal RNA antisense transcripts (PAPAS) can repress ribosomal RNA synthesis, although its role in human disease is currently unknown. The present study aimed to investigate the function of PAPAS in papillary thyroid carcinoma (PTC). PAPAS was downregulated, while the lncRNA HOXA transcript at the distal tip (HOTTIP) was upregulated in patients with PTC. PAPAS and HOTTIP were inversely associated in PTC. PAPAS overexpression led to the downregulation of HOTTIP in PTC cells, while PAPAS expression was not significantly affected by HOTTIP overexpression, suggesting that PAPAS was upstream of HOTTIP. PAPAS expression level decreased, while HOTTIP expression level increased with the increase of clinical staging. PAPAS overexpression led to the inhibition of cell proliferation, while HOTTIP overexpression increased proliferation of PTC cells, and HOTTIP overexpression decreased the effects of PAPAS overexpression. lncRNA PAPAS overexpression may inhibit tumor growth in papillary thyroid carcinoma by downregulating lncRNA HOTTIP.

Long noncoding RNA HOTTIP overexpression: A potential prognostic biomarker in prostate cancer

HOXA transcript at the distal tip (HOTTIP) is a long noncoding RNA (lncRNA), which is >200 nucleotides in length. HOTTIP expression has been demonstrated to play a crucial oncogenic role in cancer pathogenesis, and is said to be associated with poor human cancer prognosis. In prostate cancer, HOTTIP has been identified as an oncogene, but its clinicopathologic significance remains unclear. Array-based qRT-PCR was used to investigate lncRNA levels in 10 pairs of prostate cancer tissues and non-neoplastic parenchyma. Tissue microarray (TMA) was constructed using a total of 70 surgically resected prostatic adenocarcinoma tissues obtained from the Korea University Anam Hospital from 2009 to 2013. HOTTIP expression was determined by RNA in situ hybridization(ISH) and was correlated with clinicopathologic features. Increased HOTTIP expression was observed in all available prostate cancer tissue specimens compared with that in paired normal tissue. High HOTTIP expression was positively associated with bad clinicopathologic features, including higher pathologic T stage (p < 0.001), presence of extraprostatic extension (p < 0.001), seminal vesicle invasion (p < 0.001), perineural invasion (p < 0.001), and the tumor involvement of resection margin (p = 0.044). In particular, significantly increased HOTTIP expression was observed in specimens from patients in the high or very high-risk group, according to the 2018 National Comprehensive Cancer Network (NCCN) guidelines (p < 0.001). Also, patients with high HOTTIP expression showed poorer overall survival than those with low expression. In conclusion, we analytically validated the poor prognostic significance of HOTTIP overexpression and its association with bad clinicopathologic features, and present HOTTIP as a potential prognostic biomarker in prostate cancer.

Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway.

Renal cell carcinoma (RCC) is the most common malignancy of the urinary system, and it is a serious threat to human health. HOXA transcript at the distal tip (HOTTIP), located at the 5' end of the HOXA locus, is a long non-coding RNA that has been newly discovered in recent years. It has been reported to promote the development of several types of tumors. Moreover, accumulating evidence has indicated that autophagy plays an important role in tumor cell survival or death. However, whether HOTTIP affects RCC development by regulating autophagy remains unknown. In this study, we first measured HOTTIP expression in 42 paired RCC and adjacent non-tumor tissues, as well as in 4 RCC cell lines and 1 normal renal tubular epithelial cell line. Then, we selected 2 RCC cell lines to silence HOTTIP expression and 1 RCC cell line to overexpress HOTTIP, and we measured their proliferation, migration and invasion, as well as autophagy, after pretreatment with an autophagy inhibitor or inducer. In addition, we assessed the growth, metastasis and autophagy of tumors in nude mice and explored the mechanism involved. The results showed that HOTTIP expression was significantly upregulated in the RCC tissues and cell lines, and it was closely associated with TNM stage, histological grade, lymph node metastasis and patient prognosis. The in vitro and in vivo assays indicated that HOTTIP silencing inhibited RCC cell proliferation, migration and invasion and induced autophagy, and 3-MA (an autophagy inhibitor) reversed these effects. In contrast, HOTTIP overexpression and rapamycin (an autophagy inducer) yielded the opposite results. Further research revealed that HOTTIP modification could affect RCC cell autophagy via the PI3K/Akt/Atg13 signaling pathway. Our study will help in finding a potential marker for RCC diagnosis and supply a target molecule for RCC treatment.

Long non-coding RNA HOTTIP promotes prostate cancer cells proliferation and migration by sponging miR-216a-5p.

Long non-coding RNAs (lncRNAs) are a class of ncRNAs with >200 nts in length that regulate gene expression. The HOXA transcript at the distal tip (HOTTIP) lncRNA plays an important role in carcinogenesis, however, the underlying role of HOTTIP in prostate cancer (PCa) remains unknown. The aim of the present study was to evaluate the expression and function of HOTTIP in PCa. In the present study, we analyzed HOTTIP expression levels of 86 PCa patients in tumor and adjacent normal tissue by real-time quantitative PCR (qPCR). Knockdown or overexpression of HOTTIP was performed to explore its roles in cell proliferation, migration, invasion, and cell cycle. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOTTIP and miR-216a-5p in PCa cells. Our results found that HOTTIP was up-regulated in human primary PCa tissues with lymph node metastasis. Knockdown of HOTTIP inhibited PCa cell proliferation, migration, and invasion. Overexpression of HOTTIP promoted cell proliferation, migration, and invasion of PCa cells. Bioinformatics online programs predicted that HOTTIP sponge miR-216a-5p at 3′-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOTTIP could negatively regulate the expression of miR-216a-5p in PCa cells. Above all, the knockdown of HOTTIP could represent a rational therapeutic strategy for PCa.

LncRNA HOTTIP mediated DKK1 downregulation confers metastasis and invasion in colorectal cancer cells.

Recent studies highlight long non-coding RNAs (lncRNAs) as key regulators of cancer biology that contribute to carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. Previous studies demonstrated that HOTTIP could promote colorectal cancer (CRC) cell proliferation via silencing of p21 expression. However, the potential role of HOTTIP in CRC metastasis has not yet been discussed. Here, we found that HOTTIP level was significantly higher in CRC than in corresponding adjacent normal tissues, and patients with a larger tumor size, advanced pathological stage, or distant metastasis had higher HOTTIP expression. Moreover, silencing HOTTIP expression by siRNA or shRNA could inhibit CRC cell migration and invasion in vitro and in vivo, whereas HOTTIP overexpression promoted cell metastasis, as documented in the SW480 cell lines. Mechanistic analyses indicated that HOTTIP regulates CRC cell metastasis partly through the downregulation of tumor suppressor DKK1 expression. Collectively, our results suggest that tumor expression of lncRNA HOTTIP plays an important role in CRC metastasis. HOTTIP may serve as a candidate biomarker in this disease.

Long noncoding RNA HOTTIP alleviates oxygen-glucose deprivation-induced neuronal injury via modulating miR-143/hexokinase 2 pathway.

HOXA transcript at the distal tip (HOTTIP), which is a long noncoding RNA, plays an important role in multiple cancers and in coronary artery disease. Elevated microRNA-143 (miR-143) expression causes impaired glucose uptake that is responsible for the ischemic cerebral injury. However, the role and mechanism of HOTTIP in ischemic stroke are still unknown. The expression of HOTTIP and miR-143 was first detected in mouse models of transient middle cerebral artery occlusion and in primary neurons exposed to oxygen-glucose deprivation (OGD). We used gain-of function and loss-of function approaches in vitro to investigate the effect and mechanism of HOTTIP on ischemic stroke by evaluating cell viability, apoptosis, and glycolytic metabolism of neurons exposed to OGD. The HOTTIP expression was decreased, whereas miR-143 increased in experimental ischemic stroke models. Overexpression of HOTTIP by the pcDNA3.1-HOTTIP plasmid significantly increased cell viability, glucose uptake, and the expression of hexokinase 2 (HK-2) and pyruvate kinase M2 that were reduced by OGD insult. The HOTTIP overexpression also diminished OGD induced the apoptosis and the caspase-3 activity of neurons. The miR-143 mimic reversed these effects, and anti-miR-143 enhanced them. In addition, we found that HOTTIP could function as a competing endogenous RNA for miR-143 to modulate HK-2 expression. In conclusion, the HOTTIP expression was reduced in ischemic stroke. The HOTTIP overexpression attenuated OGD-induced neuronal injury and imbalanced glycolytic metabolism by sponging miR-143, resulting in the de-repression of its endogenous target HK-2. Taken together, these findings improve understanding of the pathogenesis of ischemic stroke.

Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway.

Atherosclerosis is the major cause of stroke and heart disease. However, the course and pathogenesis of atherosclerosis remains unknown. The proliferation and migration of endothelial cell play important roles in the inition and pathological progression of atherosclerosis. In this study, we demonstrated that long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) expression level was higher in coronary artery disease (CAD) tissues than in normal arterial tissues. The expression level of HOTTIP was upregulated in the proliferating endothelial cells induced by TNF-α or PDGF-BB. Ectopic expression of HOTTIP promoted endothelial cell proliferation and also increased the expression of proliferating makers cyclin D1 and PCNA. Moreover, elevated expression of HOTTIP promoted endothelial cell migration. Downregulation expression of HOTTIP suppressed endothelial cell proliferation and migration. Furthermore, we determined that overexpression of HOTTIP induced β-catenin expression and enhanced the downstream protein c-Myc expression in the endothelial cell. Ectopic expression of HOTTIP increased endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway. These results suggested that HOTTIP might manipulate the endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway.

Over-expression of the long non-coding RNA HOTTIP inhibits glioma cell growth by BRE.

BackgroundGliomas are the most common type of primary brain tumour in the central nervous system of adults. The long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) is transcribed from the 5′ tip of the HOXA locus. HOTTIP has recently been shown to be dysregulated and play an important role in the progression of several cancers. However, little is known about whether and how HOTTIP regulates glioma development.MethodsIn this study, we assayed the expression of HOTTIP in glioma tissue samples and glioma cell lines using real-time polymerase chain reaction and defined the biological functions of HOTTIP using the CCK-8 assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay) and tumour formation assay in a nude mouse model. Finally, we discovered the underlying mechanism using the Apoptosis PCR 384HT Array, Western blot, RNA immunoprecipitation (RIP) and luciferase reporter assay.ResultsHOTTIP was aberrantly down-regulated in glioma tissues and glioma cell lines (U87-MG, U118-MG, U251 and A172), and over-expression of HOTTIP inhibited the growth of glioma cell lines in vitro and in vivo. Furthermore, HOTTIP could directly bind to the brain and reproductive expression (BRE) gene and down-regulate BRE gene expression. In addition, we further verified that over-expression of the BRE gene promoted the growth of glioma cell lines in vitro. Finally, over-expression of HOTTIP significantly suppressed the expression of the cyclin A and CDK2 proteins and increased the expression of the P53 protein. However, we found that the over-expression of BRE significantly increased the expression of the cyclin A and CDK2 proteins and suppressed the expression of the P53 protein. Taken together, these findings suggested that high levels of HOTTIP reduced glioma cell growth. Additionally, the mechanism of HOTTIP-mediated reduction of glioma cell growth may involve the suppression of cyclin A and CDK2 protein expression, which increases P53 protein expression via the down-regulation of BRE.ConclusionsOur studies demonstrated that over-expression of HOTTIP promotes cell apoptosis and inhibits cell growth in U118-MG and U87-MG human glioma cell lines by down-regulating BRE expression to regulate the expression of P53, CDK2 and Cyclin A proteins. The data described in this study indicate that HOTTIP is an interesting candidate for further functional studies in glioma and demonstrate the potential application of HOTTIP in glioma therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0431-y) contains supplementary material, which is available to authorized users.

The long noncoding RNA HOXA transcript at the distal tip promotes colorectal cancer growth partially via silencing of p21 expression.

Accumulating evidence strongly suggests that dysregulation of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. However, the biological role of HOTTIP in colorectal cancer (CRC) has not yet been discussed. Here, we report that HOTTIP acts as a functional oncogene in the pathogenesis of CRC. In this study, quantitative polymerase chain reaction (qPCR) was performed to detect the expression of HOTTIP in 48 pairs of colorectal cancer samples. We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. Collectively, our results suggest that HOTTIP is involved in the progression of CRC and may provide evidence for HOTTIP being a target for therapy of this disease.

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have been demonstrated to be a critical role in cancer progression and prognosis. However, little is known about the pathological role of lncRNA HOXA transcript at the distal tip (HOTTIP) in tongue squamous cell carcinoma (TSCC) patients. The aim of this study is to measure the expression of lncRNA HOTTIP in TSCC patients and to explore the clinical significance of the lncRNA HOTTIP. The expression of lncRNA HOTTIP was measured in 86 TSCC tissues and 14 adjacent non-malignant tissues using qRT-PCR. In our study, results indicated that lncRNA HOTTIP was highly expressed in TSCC compared with adjacent non-malignant tissues (P < 0.001) and positively correlated with T stage (T1-2 vs. T3-4, P = 0.023), clinical stage (I-II stages vs. III-IV stages, P = 0.018), and distant metastasis (absent vs. present, P = 0.031) in TSCC patients. Furthermore, we also found that lncRNA HOTTIP overexpression was an unfavorable prognostic factor in TSCC patients (P < 0.001), regardless of T stage, distant metastasis, and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for TSCC patients through multivariate analysis (P = 0.023). In conclusion, increased lncRNA HOTTIP expression may be serve as an unfavorable prognosis predictor for TSCC patients. Nevertheless, further investigation with a larger sample size is needed to support our results.