Long noncoding RNA TMPO-AS1 upregulates BCAT1 expression to promote cell proliferation in nasopharyngeal carcinoma via microRNA let-7c-5p.

BACKGROUND: Long non-coding RNA (lncRNA) is a group of RNA transcripts that contribute to tumor development by post-transcriptionally regulating cancer-related genes. Nasopharyngeal carcinoma (NPC) is an epithelial tumor that occurs in the nasopharynx and is common in North Africa and Southeast Asia. The study investigated the functions of lncRNA TMPO-AS1 in NPC cell proliferation and apoptosis as well as its related competing endogenous RNA (ceRNA) mechanism. METHODS: Candidate microRNA and genes that may regulated by TMPO-AS1 were predicted with the bioinformatic tool starBase. TMPO-AS1 expression in NPC tissue, cells, nuclear part, and cytoplasmic part was measured by RT-qPCR. MTT assay, EdU assay, and flow cytometry analysis were carried out to evaluate NPC cell viability, proliferation, and apoptosis, respectively. RNA immunoprecipitation assay and luciferase reporter assay were conducted to detect the binding between TMPO-AS1 and let-7c-5p or that between let-7c-5p and BCAT1. RESULTS: TMPO-AS1 and BCAT1 showed high expression in NPC tissue and cells, while let-7c-5p was downregulated in NPC. The silencing of TMPO-AS1 suppressed NPC cell proliferation while promoting cell apoptosis. Moreover, TMPO-AS1 interacted with let-7c-5p and negatively regulated let-7c-5p expression. BCAT1 was a target of let-7c-5p and was inversely regulated by let-7c-5p in NPC cells. The repressive impact of TMPO-AS1 knockdown on NPC cell growth was countervailed by overexpressed BCAT1. CONCLUSION: TMPO-AS1 accelerates NPC cell proliferation and represses cell apoptosis by interacting with let-7c-5p to regulate BCAT1 expression.

Deciphering the oncogenic landscape: Unveiling the molecular machinery and clinical significance of LncRNA TMPO-AS1 in human cancers.

The in-depth exploration of long non-coding RNAs (lncRNAs) reveals their pivotal and diverse roles in various disorders, particularly cancer. Within this intricate landscape, thymopoietin-antisense RNA-1 (TMPO-AS1) emerges as a noteworthy instigator of oncogenesis in humans. This exhaustive review seeks to intricately unravel the present understanding of TMPO-AS1, emphasizing its molecular foundations and highlighting its clinical applications in the realm of cancer research. TMPO-AS1 consistently exhibits heightened expression across a spectrum of cancer types, encompassing lung, colorectal, breast, cervical, bladder, pancreatic, hepatocellular, gastric, ovarian, and osteosarcoma. Elevated levels of TMPO-AS1 are intricately linked to unfavorable prognoses, accompanied by distinctive clinical and pathological characteristics. Functionally, TMPO-AS1 showcases its prowess in enhancing cancer cell migration, invasion, proliferation, and orchestrating epithelial-mesenchymal transition (EMT) through a myriad of molecular mechanisms. These mechanisms entail intricate interactions with proteins, microRNAs, and intricate signaling pathways. Furthermore, TMPO-AS1 is intricately involved in regulating critical cellular processes, including apoptosis and the cell cycle. The mounting evidence converges towards the potential of TMPO-AS1 serving as a diagnostic and prognostic biomarker, further entwined with its potential role in influencing chemoresistance in cancer. This potential is underscored by its consistent associations with clinical outcomes and treatment responses. This comprehensive investigation not only consolidates our existing knowledge of TMPO-AS1's multifaceted roles but also sheds illuminating insights on its profound significance in the intricate landscape of cancer biology, paving the way for potential applications in clinical practice.

Long noncoding RNA TMPO-AS1 accelerates glycolysis by regulating the miR-1270/PKM2 axis in colorectal cancer.

BACKGROUND: Long noncoding RNA thymopoietin-antisense RNA 1 (TMPO-AS1) is recognized as a participant in cancer progression. Nevertheless, its biological function in colorectal cancer remains obscure and needs further elucidation. METHODS AND RESULTS: First, we discovered enriched TMPO-AS1 in the tumor tissues that were related to poor prognosis. TMPO-AS1 knockdown enhanced SW480 cell apoptosis but inhibited invasion, proliferation, migration, and glucose metabolism. Further, MiR-1270 is directly bound with TMPO-AS1. MiR-1270 mimics were confirmed to inhibit cell proliferation, invasion, and glucose metabolism in our study. Mechanistically, miR-1270 directly is bound with the 3' untranslated regions (3'UTR) of PKM2 to downregulate PKM2. MiR-1270 inhibitors reversed the TMPO-AS1 knockdown's effect on suppressing the tumor cell proliferation, invasion, and glycolysis, while the knockdown of PKM2 further inverted the function of miR-1270 inhibitors on the TMPO-AS1 knockdown. CONCLUSIONS: This study illustrated that TMPO-AS1 advanced the development and the glycolysis of colorectal cancer by modulating the miR-1270/PKM2 axis, which provided a new insight into the colorectal cancer therapeutic strategy.

Neuroinflammation after ischemic stroke involves INPP5D expression mediated by the TMPO-AS1-PU.1 complex.

OBJECTIVES: This study aims to explore the role of lncRNA TMPO-AS1 in ischemic stroke and corresponding mechanism. METHODS: Adult male C57BL/6 J mice were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, then TMPO-AS1 shRNA lentivirus were injected into ipsilateral striatum of mice. The neurological score and cerebral infarction volume were evaluatedHypoxia/glucose deprivation/reoxygenation (OGD/R)-induced BV2 cells were transfected with TMPO-AS1 shRNA (sh-TMPO-AS1) or together with pcDNA-INPP5D, as well as transfected with sh-PU.1 or together with pcDNA-INPP5D, then TMPO-AS1 level, the expression of PU.1 and INPP5D proteins, the secretion of inflammatory factors (TNF-α, IL-6 and IL-1ß), the levels of iNOS, CD68,Arg1 and CD206 mRNA were detected. RIP and PNA-pull down assays were used to detect the binding of TMPO-AS1 and PU.1, luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays were used to detect the binding activity of PU.1 and INPP5D. RESULTS: TMPO-AS1 level was increased in peripheral blood of ischemic stroke patients , brain tissues of MCAO/R model mice and OGD/R-induced BV2 cells. TMPO-AS1 interference inhibited the inflammation of OGD/R-induced BV2 cells. TMPO-AS1 also enhanced the nuclear accumulation of PU.1 by binding to the transcription factor PU.1, and promoted the transcriptional activation of INPP5D. The anti-inflammatory effects of TMPO-AS1 interference were reversed by INPP5D overexpression. In addition, TMPO-AS1 interference improved the infarct volume of MCAO mice, and improved sensorimotor and cognitive functions. CONCLUSION: INPP5D underexpression mediated by TMPO-AS1-PU.1 complex alleviated neuroinflammation after ischemic stroke.

A long non-coding RNA with important roles in the carcinogenesis.

Long non-coding RNAs are demonstrated to contribute to carcinogenesis. TMPO Antisense RNA 1 (TMPO-AS1) is an example of lncRNAs with crucial roles in this process. This lncRNA serves as a sponge for miR-320a, miR-383-5p, miR-329-3p, miR-126, miR-329, miR-199a-5p, miR-577, miR-4731-5p, miR-140-5p, miR-1179, miR-143-3p, miR-326, miR-383-5p, let-7c-5p, let-7g-5p, miR-199a-5p, miR-200c, miR-204-3p, miR-126-5p, miR-383-5p, miR-498, miR-143-3p, miR-98-5p, miR-140 and miR-143. It can also affect activity of PI3K/Akt/mTOR pathway. The current review summarizes the role of TMPO-AS1 in the carcinogenesis and assessment of its potential as a marker for certain types of cancers.

Long Non-Coding RNA TMPO-AS1 Promotes GLUT1-Mediated Glycolysis and Paclitaxel Resistance in Endometrial Cancer Cells by Interacting With miR-140 and miR-143.

Increased glycolysis in tumor cells is frequently associated with drug resistance. Overexpression of glucose transporter-1 (GLUT1) promotes the Warburg effect and mediates chemoresistance in various cancers. Aberrant GLUT1 expression is considered as an essential early step in the development of endometrial cancer (EC). However, its role in EC glycolysis and chemoresistance and the upstream mechanisms underlying GLUT1 overexpression, remain undefined. Here, we demonstrated that GLUT1 was highly expressed in EC tissues and cell lines and that high GLUT1 expression was associated with poor prognosis in EC patients. Both gain-of-function and loss-of-function studies showed that GLUT1 increased EC cell proliferation, invasion, and glycolysis, while also making them resistant to paclitaxel. The long non-coding RNA TMPO-AS1 was found to be overexpressed in EC tissues and to be negatively associated with EC patient outcomes. RNA-immunoprecipitation and luciferase reporter assays confirmed that TMPO-AS1 elevated GLUT1 expression by directly binding to two critical tumor suppressor microRNAs (miR-140 and miR-143). Downregulation of TMPO-AS1 remarkably reduced EC cell proliferation, invasion, glycolysis, and paclitaxel resistance in EC cells. This study established that dysregulation of the TMPO-AS1-miR-140/miR-143 axis contributes to glycolysis and drug resistance in EC cells by up-regulating GLUT1 expression. Thus, inhibiting TMPO-AS1 and GLUT1 may prove beneficial in overcoming glycolysis-induced paclitaxel resistance in patients with EC.

lncRNA TMPO antisense RNA 1 promotes the malignancy of cholangiocarcinoma cells by regulating let-7g-5p/ high-mobility group A1 axis.

Cholangiocarcinoma (CHOL) is often diagnosed at an advanced stage; therefore, exploring its key regulatory factors is important for earlier diagnosis and treatment. This study aimed to identify the mechanisms of long non-coding RNA (lncRNA) TMPO Antisense RNA 1 (TMPO-AS1), microRNA let-7 g-5p, and high-mobility group A1 (HMGA1) proteins in CHOL. Our results, through quantitative real-time PCR and Western blot detection, showed that TMPO-AS1 and HMGA1 were overexpressed while let-7 g-5p was underexpressed in CHOL. Cell function experiments in CHOL cells revealed that TMPO-AS1 knockdown inhibited cell proliferation, colony formation, and cell migration, but induced apoptosis. TMPO-AS1 knockdown also suppressed tumor growth in vivo. Together with luciferase assay and Western blotting, we found that TMPO-AS1 could sponge let-7 g-5p to promote HMGA1 expression. Moreover, HMGA1 overexpression attenuated the effect of TMPO-AS1 downregulation in CHOL cells. Overall, our findings identified the oncogenic effect of TMPO-AS1 on CHOL cells, which may put forward a novel methodology for CHOL diagnosis and therapy.

Long non-coding RNA TMPO-AS1 facilitates the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.

BACKGROUND AND AIM: Colorectal cancer, as a common malignant carcinoma in the gastrointestinal tract, has a high mortality globally. However, the specific molecular mechanisms of long non-coding RNA (lncRNA) thymopoietin antisense transcript 1 (TMPO-AS1) in colorectal cancer were unclear. METHODS: We tested the expression level of TMPO-AS1 via qRT-PCR in colorectal cancer cells, while the protein levels of branched chain amino acid transaminase 1 (BCAT1) and the stemness-related proteins were evaluated by western blot analysis. Colony formation, EdU staining, TUNEL, flow cytometry, and sphere formation assays were to assess the biological behaviors of colorectal cancer cells. Then, luciferase reporter, RIP, and RNA pull down assay were applied for confirming the combination between microRNA-98-5p (miR-98-5p) and TMPO-AS1/BCAT1. RESULTS: TMPO-AS1 was aberrantly expressed at high levels in colorectal cancer cells. Silenced TMPO-AS1 restrained cell proliferation and stemness and promoted apoptosis oppositely, while overexpressing TMPO-AS1 exerted the adverse effects. Furthermore, miR-98-5p was proven to a target of TMPO-AS1 inhibit cell progression in colorectal cancer. Additionally, BCAT1 was proved to enhance cell progression as the target of miR-98-5p, and it offset the effect of silenced TMPO-AS1 on colorectal cancer cells. CONCLUSION: TMPO-AS1 promotes the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.

LncRNA TMPO-AS1 serves as a sponge for miR-4731-5p modulating breast cancer progression through FOXM1.

OBJECTIVE: To investigate the function of IncRNA-TMPO-AS1 in breast cancer (BC) and to further explore its molecular mechanism. METHODS: TMPO-AS1, miR-4731-5p and FOXM1 were quantitatively determined using qRT-PCR. CCK-8 assays, plate cloning experiments, wound healing and Transwell assays, and flow cytometry were used to assess the biological behaviors of BC cells. Dual-luciferase reporter assays were used to assess the interactions between TMPO-AS1 and its downstream targets. The apoptosis and cell cycle-related proteins were quantitatively determined using Western blot. RESULTS: In the BC tissues and cells, TMPO-AS1 was significantly increased (P<0.05). Functional studies suggest that the knockdown of TMPO-AS1 tremendously restrains tumor cell growth and migration (P<0.05). Mechanically, TMPO-AS1 negatively regulates miR-4731-5p and influences the progression of BC through the miR-4731-5p/FOXM1 axis. CONCLUSION: LncRNA TMPO-AS1spongess miR-4731-5p to modulate BC progression through FOXM1.

LncRNA TMPO-AS1 suppresses the maturation of miR-335-5p to participate in polycystic ovary syndrome.

BACKGROUND: TMPO-AS1 is a recently characterized oncogenic lncRNA in ovarian cancer. Its role in other ovary diseases is unknown. This study explored its role in polycystic ovary syndrome (PCOS). METHODS: Follicular fluid was extracted from both PCOS patients and controls. The levels of TMPO-AS1 and mature and premature miR-335-5p were analyzed by RT-qPCR. The role of TMPO-AS1 in regulating miR-355-5p maturation in granulosa-like tumor (KGN) cells was analyzed by overexpression experiments. The interaction between TMPO-AS1 and premature miR-335-5p was analyzed by RNA pull-down assay. The subcellular location of TMPO-AS1 in KGN cells was analyzed by nuclear fractionation assay. The role of TMPO-AS1 and miR-335-5p in KGN cell proliferation was analyzed by BrdU assay. RESULTS: TMPO-AS1 was increased in PCOS, while mature miR-355-5p was decreased in PCOS. TMPO-AS1 overexpression decreased mature miR-355-5p level but increased premature miR-355-5p. TMPO-AS1 was localized in both nucleus and cytoplasm. TMPO-AS1 directly interacted with premature miR-355-5p in KGN cells. TMPO-AS1 increased KGN cell proliferation while miR-355-5p decreased cell proliferation. The co-transfection assay showed that TMPO-AS1 reduced the suppressive effects of miR-355-5p on cell proliferation. CONCLUSIONS: TMPO-AS1 might suppress miR-335-5p maturation to participate in PCOS.

The Emerging Role of Thymopoietin-Antisense RNA 1 as Long Noncoding RNA in the Pathogenesis of Human Cancers.

Long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of multiple human cancers. An accumulating body of researches have investigated thymopoietin antisense RNA 1 (TMPO-AS1) as a newly discovered lncRNA, which functions as an oncogenic lncRNA that is upregulated in various human malignancies and associated with poor prognosis. Many studies have detected abnormally high expression levels of TMPO-AS1 in multiple cancers, such as lung cancer, breast cancer, colorectal cancer (CRC), hepatocellular carcinoma, CRC, gastric cancer, ovarian cancer, thyroid cancer, esophageal cancer, Wilms tumor, cervical cancer, retinoblastoma, bladder cancer, osteosarcoma, and prostate cancer. TMPO-AS1 has been subsequently demonstrated to play a pivotal role in tumorigenesis and progression. The aberrantly expressed TMPO-AS1 acts as a competing endogenous RNA (ceRNA) that inhibits miRNA expression, thus activating the expression of downstream oncogenes. This study comprehensively summarizes the aberrant expressions of TMPO-AS1 as reported in the current literature and explains the relevant biological regulation mechanisms in carcinogenesis and tumor progression. Corresponding studies have indicated that TMPO-AS1 has a potential value as a promising biomarker or a target for cancer therapy.

ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is notorious for its poor prognosis. Increasing evidence has demonstrated that semaphorin 3F (SEMA3F) plays key roles in initiation and progression of several types of human cancer. However, the specific role and mechanism of SEMA3F in HCC remains not fully determined. In this study, we first performed pan-cancer analysis for SEMA3F's expression and prognosis using The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) data and found that SEMA3F might be a potential oncogene in HCC. Subsequently, noncoding RNAs (ncRNAs) contributing to SEMA3F overexpression were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. Finally, the TMPO-AS1/SNHG16-let-7c-5p axis was identified as the most potential upstream ncRNA-related pathway of SEMA3F in HCC. Moreover, SEMA3F level was significantly positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. Collectively, our findings elucidated that ncRNAs-mediated upregulation of SEMA3F correlated with poor prognosis and tumor immune infiltration in HCC.

Long non-coding RNA TMPO-AS1 facilitates chemoresistance and invasion in breast cancer by modulating the miR-1179/TRIM37 axis.

Breast cancer has become the most common female tumor in the world. Although great progress has been made in the past decade, the treatment of advanced breast cancer remains unsatisfactory. An increasing number of reports have indicated that long non-coding RNAs (lncRNAs) have a pivotal role in chemoresistance as potential oncogenes in numerous types of cancer. However, the precise mechanisms underlying the action of lncRNAs in breast cancer resistance to chemotherapy have yet to be fully elucidated. In the present study, the function and molecular mechanisms of the lncRNA TMPO-antisense RNA 1 (AS1) in terms of its resistance to docetaxel (DOC) were explored in the MDA-MB-231 and MCF7 breast cancer cell lines. The results obtained suggested that TMPO-AS1 was markedly upregulated in DOC-resistant breast cancer cells compared with the sensitive breast cancer cells. Functionally, TMPO-AS1-knockdown sensitized MDA-231/DOC and MCF-7/DOC cells to DOC and suppressed cell invasion, with increased rates of DOC-induced apoptosis. Mechanistically, TMPO-AS1-downregulation induced DOC-sensitivity in breast cancer cells via depleting tripartite motif-containing protein 37 (TRIM37) by sponging microRNA (miR)-1179. Taken together, the present study has revealed the existence of a novel TMPO-AS1/miR-1179/TRIM37 molecular axis conferring DOC resistance of breast cancer cells, thereby suggesting a promising novel therapeutic target for breast cancer.

The Long Non-coding RNA TMPO-AS1 Promotes Bladder Cancer Growth and Progression via OTUB1-Induced E2F1 Deubiquitination.

Background: Increasing evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis and progression. TMPO antisense RNA 1 (TMPO-AS1) has been found to be involved in several cancers by acting as a competing endogenous RNA. However, the potential roles of TMPO-AS1 in bladder cancer (BC) and the potential interactions with proteins remain poorly understood. Methods: The expression of the lncRNA TMPO-AS1 was evaluated via bioinformatic analysis and further validated by quantitative real-time PCR (qRT-PCR). Loss- and gain-of-function assays were performed to determine the biological functions of TMPO-AS1 in BC cell proliferation, migration, and invasion. Moreover, chromatin immunoprecipitation, Western blotting, and fluorescence in situ hybridization, as well as RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays, were conducted to explore the upstream and downstream molecules interacting with TMPO-AS1. Results: TMPO-AS1 is upregulated in BC. Functional experiments demonstrated that TMPO-AS1 promotes cell proliferation, migration, and invasion in BC and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization; therefore, TMPO-AS1 promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner. Conclusions: Our study is the first to uncover the novel TMPO-AS1/E2F1 positive regulatory loop important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.

TMPO-AS1 Regulates the Aggressiveness-Associated Traits of Nasopharyngeal Carcinoma Cells Through Sponging miR-320a.

BACKGROUND: Previous evidence demonstrates that the long non-coding RNA (lncRNA) TMPO antisense RNA 1 (TMPO-AS1) is involved in the aggressiveness of several cancers. Nevertheless, its functions in nasopharyngeal carcinoma (NPC) are unclear. METHODS: qRT-PCR was used to evaluate the levels of TMPO-AS1 and miR-320a in NPC tissues. Furthermore, the growth and invasiveness of NPC cells were evaluated by colony formation and Transwell assays. The protein expression ofSRY-Box Transcription Factor 4 (SOX4) was observed by Western blotting and immunohistochemistry. Bioinformatic prediction and luciferase reporter assays were used to explore the interaction between miR-320a and TMPO-AS1. The transplanted model was employed to disclose the interference of TMPO-AS1 in the tumor growth of NPC cells in vivo. RESULTS: We found that TMPO-AS1 was distinctly upregulated in NPC. Downregulation of TMPO-AS1 restrained aggressiveness-associated traits in NPC cells. Nevertheless, upregulation of TMPO-AS1 yielded the opposite results. Further studies revealed that lncRNA TMPO-AS1 acts as a "sponge" for miR-320a, resulting in increased levels of SOX4 in NPC cells. Finally, TMPO-AS1 silencing suppressed tumor growth of NPC cells in vivo. CONCLUSION: Collectively, these results reveal the presence of a novel TMPO-AS1/miR-320a/SOX4 pathway associated with NPC progression, suggesting that lncRNA TMPO-AS1 may be a potential therapeutic target for NPC.

Long noncoding TMPO antisense RNA 1 promotes hepatocellular carcinoma proliferation and epithelial-mesenchymal transition by targeting the microRNA-126-3p/LRP6/ß-catenin axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a central role in the pathogenesis of various tumors, including hepatocellular carcinoma (HCC). TMPO antisense RNA 1 (TMPO-AS1) has been reported in many tumors. Nevertheless, the underlying mechanism whereby TMPO-AS1 influences HCC remains unclear. Our research aimed to reveal the molecular mechanism governing the function of TMPO-AS1 in HCC. METHODS: TMPO-AS1 expression levels in HCC tissues/cells were evaluated using reverse transcriptase-polymerase chain reaction. The effect of TMPO-AS1 on the progression of HCC was observed by Cell Counting Kit-8 (CCK8), clone formation, wound healing, and transwell. The direct interaction between TMPO-AS1 and microRNA (miR)-126-3p was observed using a dual-luciferase reporter. RESULTS: We found TMPO-AS1 expression to be remarkably higher in HCC specimens and associated with poor prognosis. Silencing of TMPO-AS1 not only inhibited HCC cell proliferation but also significantly reduced epithelial-to-mesenchymal transition-induced invasion and migration to a remarkable degree. According to the results from the online database analysis tools implemented to identify if TMPO-AS1 could target miR-126-3p, we found that miR-126-3p had a negative relationship with TMPO-AS1 in HCC specimens. Meanwhile, the luciferase reporter assay confirmed that TMPO-AS1 could directly act on miR-126-3p. Moreover, the silencing of miR-126-3p dramatically abolish the inhibitive influence of sh-TMPO-AS1 on HCC development. CONCLUSIONS: Our research demonstrated that TMPO-AS1 acts as a sponge for the tumor suppressor miR-126-3p in HCC and promotes the expression of LRP6 indirectly. Taken together, our results show that TMPO-AS1 may be regarded as a novel therapeutic target in the treatment of liver cancer.

Long noncoding RNA TMPO-AS1/miR-126-5p/BRCC3 axis accelerates gastric cancer progression and angiogenesis via activating PI3K/Akt/mTOR pathway.

BACKGROUND AND AIM: Gastric cancer (GC) is an aggressive tumor featured by uncontrolled cell proliferation and metastasis. In recent years, long noncoding RNAs (lncRNAs) act as crucial regulators and biological markers in multiple cancers. LncRNA TMPO-AS1 has been revealed to be an oncogene in some cancers. Nevertheless, there is little known about the biological role of TMPO-AS1 in GC. METHODS: Reverse transcription-quantitative polymerase chain reaction analysis was used to examine the expression level of TMPO-AS1 in GC tissues and cells. Cell Counting Kit-8, colony formation, wound healing assays, and western blot analysis were performed to determine the role of TMPO-AS1 in GC cells. RNA pull-down, luciferase reporter, and RNA immunoprecipitation assays were used to test the interaction among TMPO-AS1, miR-126-5p, and BRCC3. RESULTS: TMPO-AS1 was highly expressed in GC tissues and cells. Upregulated TMPO-AS1 was closely associated with adverse prognosis of GC patients. Functional assays showed that TMPO-AS1 promoted GC cell proliferation, migration, and angiogenesis. Furthermore, it was found that TMPO-AS1 acted as a competing endogenous RNA for miR-126-5p to upregulate BRCC3 expression. Rescue assays revealed that TMPO-AS1 facilitated cellular progression of GC by sponging miR-126-5p and upregulating BRCC3. In addition, we found that the effects of the TMPO-AS1/miR-126-5p/BRCC3 axis on GC cell progression were related to the PI3K/Akt/mTOR pathway. CONCLUSIONS: Our study demonstrated that the TMPO-AS1/miR-126-5p/BRCC3 axis was involved in GC progression via the regulation of PI3K/Akt/mTOR pathway, which might provide a potential therapeutic strategy for GC.

TMPO-AS1, a Novel E2F1-Regulated lncRNA, Contributes to the Proliferation of Lung Adenocarcinoma Cells via Modulating miR-326/SOX12 Axis.

BACKGROUND: TMPO-AS1, an antisense lncRNA located at human chromosome 12p23.1, has been identified as an oncogene involved in cell proliferation in various cancers, including LUAD. In this study, we aimed to explore the novel molecular mechanism of TMPO-AS1 underlying LUAD growth. MATERIALS AND METHODS: The transcription levels of TMPO-AS1, miR-326, and SOX12 in LUAD tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). The cell proliferation ability was evaluatect 3d by cell counting kit-8 (CCK-8) assay. Cell cycle and apoptosis analysis was assessed by flow cytometry. The target relationship among TMPO-AS1, miR-326, and SOX12 and promoter activity of TMPO-AS1 was measured using dual-luciferase reporter assay. The protein levels of SOX12 in LUAD cells were determined by Western blot. ChIP-qPCR assay was performed to validate the direct binding between E2F1 and TMPO-AS1 promoter. RESULTS: TMPO-AS1 was up-regulated in LUAD tissues as well as cell lines. Boosted TMPO-AS1 expression was positively correlated with poor prognosis and pathological stage in LUAD. Down-regulation of TMPO-AS1 could restrain the proliferation of LUAD cells through arresting the cell cycle at G0/G1 phase and inducing apoptosis in vitro. Mechanically, we demonstrated that TMPO-AS1 could modulate the proliferation of LUAD cells through increasing SOX12 expression level via sponging miR-326 in accordance with bioinformatics analysis and experimental validation. Furthermore, we identified that TMPO-AS1 could be activated by E2F transcription factor 1 (E2F1) as a novel target gene. CONCLUSION: TMPO-AS1 can modulate LUAD cell proliferation through E2F1/miR-326/SOX12 pathway.

LncRNA TMPO-AS1 Promotes Proliferation and Invasion by Sponging miR-383-5p in Glioma Cells.

PURPOSE: Glioma is one of the most common malignant tumors affecting human health. Long non-coding RNA (lncRNA) TMPO-AS1 participates in the pathogenesis of various cancers. However, the role of lncRNA TMPO-AS1 in glioma remains largely unknown. This study aims to uncover the role of TMPO-AS1 and explore its potential mechanism in glioma. METHODS: Expression levels of TMPO-AS1 and miR-383-5p in glioma cell lines were measured by real-time quantitative PCR (RT-qPCR). CCK-8, colony formation, wound-healing, and Transwell assays were conducted to determine cell proliferation, migration and invasion abilities, respectively. Western blotting was applied to detect the expression of corresponding proteins. Immunofluorescence assay was performed to measure the expression of Ki67. The binding condition between TMPO-AS1 and miR-383-5p was verified by dual-luciferase reporter assay. RESULTS: We found that TMPO-AS1 was up-regulated while miR-383-5p was down-regulated in glioma cell lines, and knockdown of TMPO-AS1 significantly suppressed glioma cell proliferation, migration and invasion abilities. miR-383-5p was demonstrated to be a direct target of TMPO-AS1. Besides, inhibition of miR-383-5p abolished the effects of TMPO-AS1 knockdown on glioma cells. CONCLUSION: In summary, our study revealed that inhibition of lncRNA TMPO-AS1 could suppress glioma progression through targeting miR-383-5p. TMPO-AS1 might be used as a therapeutic target for glioma treatment.

LncRNA TMPO-AS1 Aggravates the Development of Hepatocellular Carcinoma via miR-429/GOT1 Axis.

BACKGROUND: Hepatocellular carcinoma (HCC), featuring uncontrolled proliferation and migration of tumor cells, is one of the most serious malignancies with high morality. An increasing number of evidences have demonstrated that long noncoding RNAs (lncRNAs) are involved in the progression of multiple cancers. It has been acknowledged that lncRNA TMPO-AS1 plays an oncogenic role in diverse cancers. METHODS: Reverse transcription­quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of TMPO-AS1, miR-429 and GOT1 in HCC tissues and cell lines. Cell viability, proliferation, apoptosis, and stemness characteristics were detected by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, sphere formation and western blot assays, separately. The relationship among TMPO-AS1, miR-429 and GOT1 was predicted by starBase database and confirmed using luciferase reporter and RNA pull-down assays. RESULTS: In this study, our findings revealed that TMPO-AS1 expression was upregulated in HCC tissues and cell lines. TMPO-AS1 aggravated HCC progression via promoting cell proliferation, stemness as well as suppressing cell apoptosis. Further, molecular mechanism exploration discovered that TMPO-AS1 functioned as a molecular sponge for miR-429 and GOT1 served as a downstream target gene of miR-429 in HCC. Furthermore, there was a negative relationship between GOT1 and miR-429 as well as a positive correlation between GOT1 and TMPO-AS1 in HCC. Rescue assays suggested that overexpression of GOT1 partially reversed the inhibitory effects of TMPO-AS1 knockdown on HCC progression. CONCLUSIONS: Taken together, these findings indicated that TMPO-AS1 acted as a tumor motivator to expedite HCC progression via targeting miR-429/GOT1 axis, which may provide a fresh treatment strategy for HCC.