Tumor Suppressor In Cervical Cancer Research Articles

Long non-coding RNA MLLT4 antisense RNA 1 induces autophagy to inhibit tumorigenesis of cervical cancer through modulating the myosin-9/ATG14 axis

The regulatory mechanism of long non-coding RNAs (lncRNAs) in autophagy is as yet not well established. In this research, we show that the long non-coding RNA MLLT4 antisense RNA 1 (lncRNA MLLT4-AS1) is induced by the MTORC inhibitor PP242 and rapamycin in cervical cells. Overexpression of MLLT4-AS1 promotes autophagy and inhibits tumorigenesis and the migration of cervical cancer cells, whereas knockdown of MLLT4-AS1 attenuates PP242-induced autophagy. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between MLLT4-AS1 and other associated targets, such as myosin-9 and autophagy-related 14(ATG14). MLLT4-AS1 was upregulated by H3K27ac modification with PP242 treatment, and knockdown of MLLT4-AS1 reversed autophagy by modulating ATG14 expression. Mechanically, MLLT4-AS1 was associated with the myosin-9 protein, which further promoted the transcription activity of the ATG14 gene. In conclusion, we demonstrated that MLLT4-AS1 acts as a potential tumor suppressor in cervical cancer by inducing autophagy, and H3K27ac modification-induced upregulation of MLLT4-AS1 could cause autophagy by associating with myosin-9 and promoting ATG14 transcription.

Role of SLC5A8 as a Tumor Suppressor in Cervical Cancer.

The SLC5A8 gene is silenced in various types of cancer, including cervical cancer; we recently demonstrated that the SLC5A8 gene is also silenced in cervical cancer by hypermethylation of the CpG island in the gene promoter. This study aims to analyze whether SLC5A8 could be a tumor suppressor in cervical cancer. After ectopic expressing SLC5A8 in the HeLa cell line, we evaluated its effects on cell behavior both in vitro and in vivo by Confocal immunofluorescence, cell proliferation, migration assays, and xenograft transplants. Overexpression of SLC5A8 in the HeLa cell line decreased its proliferation by arresting cancer cells in the G1 phase and inhibiting cellular migration. Furthermore, we observed that pyruvate increased the SLC5A8 effect, inducing S-phase arrest and inhibiting the entry into mitosis. SLC5A8 decreased tumor growth in xenograft transplants, significantly reducing the volume and tumor weight at 35 days of analysis. In summary, our results indicate that SLC5A8 has a role as a tumor suppressor in cervical cancer.

MiR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer.

Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.

MiR-29a Function as Tumor Suppressor in Cervical Cancer by Targeting SIRT1 and Predict Patient Prognosis [Retraction

[This retracts the article DOI: 10.2147/OTT.S218043.].

Hsa_circ_0000078 Regulates miR-205-5p/EREG Pathway to Inhibit Cervical Cancer Progression.

It is well established that circular RNAs (circRNAs) play a role in tumor initiation and tumorigenesis. The goal of this study was to reveal the detailed functions and regulatory mechanisms of circ_0000078 in cervical cancer (CC). Circ_0000078, miR-205-5p, and epiregulin (EREG) mRNA expression levels were examined using RT-qPCR. Western blotting was performed to quantify EREG protein. Cell proliferation, apoptosis, migration, and invasion were examined by performing CCK-8, caspase 3 activity, wound healing, and transwell assays, respectively. The effect of circ_0000078 on tumor growth in vivo was confirmed in a xenograft model. The putative relationship between miR-205-5p and circ_0000078 or EREG, as predicted by bioinformatics analysis, was evaluated by dual-luciferase and RNA immunoprecipitation assays. Aberrant downregulation of circ_0000078 and EREG as well as upregulation of miR-205-5p were observed in cervical tumor samples and cancer cells. Ectopic expression of circ _0000078 not only restrained cancer cell growth, survival, migration, and invasiveness, but also decelerated tumor formation and development in a mouse model. miR-205-5p, acts as a target of circ_0000078 and directly binds to EREG to repress its expression. Overexpression of miR-205-5p reversed the inhibitory effects of circ_0000078 upregulation on cancer cell behavior and also partially abolished the anti-cancer effects of EREG upregulation in vitro. Circ_0000078 inhibits the growth of cancer by interfering with the miR-205-5p/EREG network, acting as a tumor suppressor in CC. These results provide a better understanding of the pathogenesis of this disease.

RASAL2 acts as a tumor suppressor in cervical cancer cells

<b>Background: </b>This study was designed to investigate the roles of RASAL2 in cervical cancer (CC). <b>Methods:</b> Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and June 2014. Real-time polymerase chain reaction and western blotting were performed to analyze the expression of RASAL2 mRNA and protein in these tissues, CC cell lines, and normal cervical cells. Over-expression and silencing of RASAL2 were induced after transfection, and the migration, invasion, and proliferation of the CC cell lines were examined. <b>Results:</b> RASAL2 mRNA and protein expressions were significantly down-regulated in CC tissues and cell lines than in adjacent tissues and normal cervical cells, respectively. While low RASAL2 expression correlated with advanced stage and metastasis of CC, its over-expression significantly inhibited proliferation and metastasis of CC cells and induced apoptosis. Under <i>in vitro</i> conditions, silencing of RASAL2 expression could significantly increase the proliferation, invasion, and migration of CC cells. <b>Conclusion:</b> RASAL2 functioned as a tumor suppressor in CC, and was down-regulated in CC tissue samples and cell lines. tumor suppressor in CC, and was down-regulated in CC tissue samples and cell lines.

Human papillomavirus 16 E6/E7 contributes to immune escape and progression of cervical cancer by regulating miR-142–5p/PD-L1 axis

Persistent infection of human papillomavirus (HPV) and immune escape are the main causes of cervical cancer. E6/E7 encoded by HPV16 may be closely related to carcinogenesis. HPV infection may upregulate PD-L1 expression, resulting in immune escape and cervical cancerigenesis. Evidence indicates that miRNAs may mediate the regulation of E6/E7 on PD-L1. Therefore, we aimed to screen the miRNA, and further verify its expression and functions. Bioinformatics approaches were used to screen the miRNAs that mediate the regulation of E6/E7 on PD-L1. The expression of the miRNA and PD-L1 in HPV+ and HPV− cervical cancer cells were compared, and the effect of E6E7 on them was evaluated. Then, the effect of the miRNA on PD-L1 was assessed by the Gain- and Loss-of-function test. Finally, in vivo experiments were conducted to verify the effects of the miRNA on tumor growth and survival of tumor-bearing mice. Six miRNAs were screened, of which miR-142–5p was identified. MiR-142–5p was downregulated and PD-L1 was upregulated in HPV− cells after transfection of E6, E7, or E6/E7. The rescue test showed that the upregulation of miR-142–5p attenuated the effect of E6/E7 on PD-L1. The reverse relationship between PD-L1 and miR-142–5p was confirmed. In vivo experiments suggest that miR-142–5p upregulation inhibits the growth of the transplanted tumors by targeting PD-L1. MiR-142–5p acts as a tumor suppressor in cervical cancer. HPV16 E6E7 may promote the immune escape of cervical cancer cells by regulating the miR-142–5p/PD-L1 axis. Using miR-142–5p in tumor immunotherapy as a new strategy is proposed.

RacGAP1 promotes the malignant progression of cervical cancer by regulating AP-1 via miR-192 and p-JNK

Cervical cancer (CC) is the most frequently diagnosed genital tract cancer in females worldwide. Rac GTPase-activating protein 1 (RacGAP1) is one of the specific GTPase-activating proteins. As a novel tumor protooncogene, overexpression of RacGAP1 was related to the occurrence of various tumors, but its function in CC is still unclear. In this study, bioinformatics analyses showed that RacGAP1 might be a key candidate gene in the progression of CC. RacGAP1 was significantly overexpressed in CC tissues. High RacGAP1 expression was positively associated with poor prognosis. Downregulating RacGAP1 significantly inhibited the proliferation, migration, and invasion of CC cells, while overexpressing RacGAP1 had the opposite effects. Further research showed that miR-192, which plays as a tumor suppressor in CC, was identified as a downstream target of RacGAP1 in CC cells. miR-192 inhibition could partially rescue the decrease in cell proliferation, migration, and invasion caused by RacGAP1 downregulation. In opposite, miR-192 overexpression could decrease the promotion of malignant progression caused by RacGAP1 upregulation. Mechanism studies revealed that RacGAP1 could regulate the expression and phosphorylation of c-Jun, which was the component of AP-1, via miR-192 and p-JNK separately. These findings suggested that RacGAP1 promoted tumorigenicity, migration, and invasion of CC. Therefore, it represented a potential novel prognostic marker in CC and may probably be a therapeutic target.

MicroRNA-106b-5p (miR-106b-5p) suppresses the proliferation and metastasis of cervical cancer cells via down-regulating fibroblast growth factor 4 (FGF4) expression.

This study aims to investigate the function and mechanism of microRNA-106b-5p (miR-106b-5p) in cervical cancer (CC). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine miR-106b-5p expression in CC tissues and normal gastric tissues. Cell counting kit-8 (CCK-8) and colony formation assays were used to analyze the regulatory effects of miR-106b-5p on CC cells' proliferative ability. Wound healing and Transwell assays were conducted to detect the effects of miR-106b-5p on cell migration and invasion. Besides, TargetScan was used to predict the potential target genes of miR-106b-5p. The interaction between miR-106b-5p and fibroblast growth factor 4 (FGF4) was proved by qRT-PCR, Western blot, and dual-luciferase reporter gene assay. MiR-106b-5p expression was down-regulated in CC tissues compared to non-tumorous tissues. The expression of miR-106b-5p was associated with the lymphatic node metastasis, FIGO stage and differentiation of CC. Functional assays revealed that miR-106b-5p overexpression suppressed CC cell proliferation, migration and invasion while miR-106b-5p inhibitor had the opposite effects. In addition, FGF4 was identified as a target gene of miR-106b-5p, and FGF could be negatively regulated by miR-106b-5p. MiR-106b-5p may serve as a tumor suppressor in CC, which can inhibit CC growth and metastasis by down-regulating FGF4 expression.

Down-regulated Circ_0000190 promotes cervical cancer by facilitating the activity of proto-oncogene protein EIF4E

ABSTRACT Circular RNAs (circRNAs), a new class of non-coding RNAs, have been recently confirmed to regulate cell development, functions and certain types of pathological responses. In addition, it has been proved that circ_0000190 can serve as a tumor suppressor in several cancers. However, the underlying mechanism and biological functions of it in cervical cancer (CC) remain to be revealed. In our study, relative expression of indicated molecules was detected by RT-qPCR analysis. Loss-of-function and gain-of-function experiments were conducted to detect cell functions. Mechanism experiments including RIP assay, luciferase reporter assay and pull down assay were applied to verify the interaction among the indicated molecules. Overexpressed circ_0000190 attenuated CC progression in vitro and in vivo. Circ_0000190 functioned through the modulation of miR-1252-5p/EIF4EBP2 axis. Rescue experiments found that miR-1252-5p overexpression or EIF4EBP2 knockdown could reverse the influence on CC cells caused by circ_0000190 overexpression. Interestingly, it was found that EIF4EBP2 could bind to proto-oncogene eIF4E and prevent eIF4E from forming into complex and functioning. Circ_0000190 served as a tumor suppressor in CC and down-regulated circ_0000190 expression could weaken the binding ability of EIF4EBP2 to eIF4E thus leading to CC tumorigenesis. In our investigation, a novel tumor suppressive gene circ_0000190 was recognized, which could be treated as a promising biomarker for the diagnosis of CC.

Downregulation of miR-599 predicts poor outcome in cervical cancer patients and promotes the progression of cervical cancer

ObjectiveCervical cancer remains a leading cause of gynecological cancer-related death. In this study, we aimed to investigate the expression pattern of miR-599 and its prognostic significance in cervical cancer. Materials and methodsThe RT-qPCR analysis was used to detect the expression levels of miR-599 in cervical cancer tissues and cell lines. The association between miR-599 expression and clinical characteristics of cervical cancer patients was analyzed using the χ2 test. The Kaplan–Meier analysis and multivariate Cox proportional hazards model were used to explore the prognostic significance of miR-599. Then, CCK-8 assays, transwell migration, and invasion assays were used to assess the effects of miR-599 on tumor cell proliferation, migration, and invasion of cervical cancer cells, respectively. ResultsmiR-599 expression was significantly downregulated in cervical cancer tissues and cells compared with non-cancerous tissues and HaCaT cells, respectively. Statistical analysis revealed that miR-599 expression was associated with lymph node metastasis and FIGO stage. The miR-599 expression was an independent prognostic factor for overall survival. Functionally, overexpression of miR-599 suppressed cell proliferation, migration, and invasion of cervical cancer cells, while downregulation of miR-599 had opposite effects. ConclusionmiR-599 acts as a tumor suppressor in cervical cancer that inhibiting cell proliferation, migration, and invasion of cervical cancer cells, suggesting that miR-599 may be a potential prognostic biomarker and novel targeted strategy for cervical cancer.

Functional New Transcription Factors (TFs) Associated with Cervical Cancer.

The goal of this research was to find noval transcription factors (TFs) that are involved in cervical carcinogenesis. The Gene Expression Omnibus (GEO) database was utilized to analyze ten cervical cancer datasets using the Robust Rank Aggregation (RRA) technique. Survival and differential expression were validated using GEPIA (Gene Expression Profiling Interactive Analysis). The transcriptional regulatory network and putative targets were built using Cytoscape. A real-time PCR (quantitative real-time polymerase chain reaction) experiment was used to confirm the mRNA expression. Using public cervical cancer single-cell RNA-sequencing (scRNA-seq), bulk TCGA-CESC RNA-seq, and microarray datasets, coexpression correlations between putative targets and TFs were confirmed. After combining the results of 10 datasets, 8 TFs, including EMX2 (Empty Spiracles Homeobox 2), were chosen among 385 robust DEGs. In the normal female reproductive tract, EMX2 is extensively expressed, but it is reduced in cervical cancer. Overexpression EMX2 suppresses the proliferation of HeLa cells. 12 potential targets of EMX2 were selected. Our research has revealed evidence that EMX2 acted as a tumor suppressor in cervical cancer and PDZRN3 might be possible target of EMX2 in cervical cancer. It might be a therapeutic target in the future.

Angiopoietin-like 3 (ANGPTL3) drives cell proliferation, migration and angiogenesis in cervical cancer via binding to integrin alpha v beta 3

ABSTRACT Angiopoietin-like 3 (ANGPTL3) has been uncovered to play an oncogenic role in several kinds of human malignancies. Nevertheless, whether ANGPTL3 functions in cervical cancer (CC) has not yet been reported. This paper is intended to explore the impact of ANGPTL3 on CC cells and elucidate the potential mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to analyze the ANGPTL3 expression. Western blot was also performed to examine integrin αvβ3 protein level. Cell proliferation was evaluated by MTT assay, EdU staining and Western blot analysis. In addition, the migratory and invasive abilities of cells were, respectively, estimated by wound healing and transwell assays. Tube formation assay was performed to determine endothelial cell angiogenesis. Levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) were measured by ELISA. As a result, ANGPTL3 expression was significantly higher in CC cells relative to that in normal cervical cells. Silencing of ANGPTL3 suppressed cell proliferation, migration and invasion. Besides, downregulation of ANGPTL3 inhibited human umbilical vein endothelial cell (HUVEC) angiogenesis and repressed protein level of integrin alpha v beta 3 (αvβ3). Upregulation of αvβ3 offsets the inhibitory effect of ANGPTL3 on proliferation, migration and invasion in CC cells. Upregulated expression of αvβ3 promoted blood vessel formation and secretions of VEGF and VEGFR2. In conclusion, ANGPTL3 silencing may serve as a tumor suppressor in CC through integrin αvβ3, which provides a potentially novel therapeutic target for patients with CC.

Circular RNA hsa_circ_0000730 restrains cell proliferation, migration, and invasion in cervical cancer through miR-942-5p/PTEN axis.

Circular RNAs (circRNAs) play prominent roles in regulating the progression of cancers. This study is aimed to decipher the role of hsa_circ_0000730 in cervical cancer (CC).The differentially expressed circRNAs of CC were screened out from the Gene Expression Omnibus database. qRT-PCR was used to detect circ_0000730 expression in CC tissues and cell lines, and the Kaplan-Meier curve was adopted to figure out the relationship between circ_000730 expression and the overall survival time of CC patients. BrdU assay and Tanswell assay were utilized to examine the proliferation, migration, and invasion of CC cells. Western blot was adopted to detect PTEN protein expression. Bioinformatics analysis and dual-luciferase reporter assay were used to examine the target relationship between miR-942-5p and circ_0000730 or PTEN, respectively.Circ_0000730 was among the differentially expressed circRNAs in CC. Circ_0000730 was significantly down-regulated in the cancer tissues of 50 CC patients and CC cell lines. Additionally, underexpression of circ_0000730 was associated with the shorter survival time of CC patients. Gain- and loss-of-function assays highlighted that circ_0000730 significantly inhibited the proliferation, migration, and invasion of CC cells. Mechanistically, miR-942-5p was identified as a downstream target of circ_0000730, and circ_0000730 could positively regulate PTEN expression via repressing miR-942-5p in CC cells.Circ_0000730 inhibits the proliferation, migration, and invasion of CC cells via regulating miR-942-5p/PTEN axis. Circ_0000730 probably acts as a tumor suppressor in CC, and it may be a candidate target for the treatment of CC.

T-box transcription factor TBX1, targeted by microRNA-6727-5p, inhibits cell growth and enhances cisplatin chemosensitivity of cervical cancer cells through AKT and MAPK pathways

ABSTRACT Cervical cancer (CC) is the fourth most common cancers among women worldwide. T-box transcription factor 1 (TBX1), a member of the T-box family, has anti-tumor effects in some types of cancer, but its role in CC is yet unknown. The aim of this study is to investigate the functions and underlying mechanisms of TBX1 in CC. Online database UALCAN showed that TBX1 was down-regulated in CC tissues compared with normal tissues and patients with lower TBX1 expression level had a poor prognosis. TBX1 overexpression significantly decreased the proliferation, migration, and invasion of Hela and SiHa cells. Conversely, cell apoptosis and chemosensitivity to cisplatin were promoted in TBX1-overexpressing CC cells. Moreover, up-regulation of TBX1 inhibited both AKT and MAPK signaling pathways. Furthermore, dual luciferase report assay indicated that TBX1 could directly bind to miR-6727-5p. In addition, TBX1 expression was inhibited by miR-6727-5p mimic and up-regulated by miR-6727-5p inhibitor. Knockdown of TBX1 reversed the inhibitory effect of the miR-6727-5p inhibitor on CC cells. This study demonstrates that TBX1, a target gene of miR-6727-5p, acts as a tumor suppressor in CC, indicating that TBX1 may be a new target for CC therapy.

MiR‑34c‑5p targets Notch1 and suppresses themetastasis and invasion of cervical cancer.

Micro (mi)RNAs are crucial participants in the progression of cervical cancer (CC). Growing evidence indicates that miRNA (miR)-34c-5p is a pivotal tumor suppressor in numerous types of cancer and its functions in CC require further investigating. The present study demonstrated that there was a decreased level of miR-34c-5p in CC-associated cell lines compared with healthy control samples. It also demonstrated that miR-34c-5p targeted Notch1 and suppressed CC progression. Dual-Luciferase reporter assays verified the targeted relationship of miR-34c-5p and Notch1. The expression of Notch1 in HeLa cells was markedly reduced following miR-34c-5p overexpression and the proliferation, migration and invasion of HeLa cells were reduced although apoptosis was accelerated. However, overexpression of miR-34c-5p was reversed following the addition of Notch1, which supported the finding of the targeted relationship between miR-34c-5p and Notch1. Flow cytometry demonstrated that miR-34c-5p inhibited the proliferation of HeLa cells while accelerating apoptosis. The present study concluded that miR-34c-5p was a tumor suppressor in CC and may be a novel measure for the future treatment of CC.

Long noncoding RNA LINC00657 inhibits cervical cancer development by sponging miR-20a-5p and targeting RUNX3.

Long noncoding RNAs act essential regulators in cervical cancer progression. Our study aimed to investigate the underlying function and molecular mechanisms of LINC00657 in cervical cancer. QRT-PCR results indicated that LINC00657 was significantly decreased in cervical cancer. Gain-and loss-of-function experiments were performed in SiHa and HeLa. Functional assays demonstrated that LINC00657 inhibited cervical cancer cell growth, migration and invasion. Moreover, miR-20a-5p was confirmed as a target of LINC00657. Furthermore, miR-20a-5p promoted the development of cervical cancer via targeting RUNX3. DR5 acts as a vital promoter in activating NK cells and is a downstream target of RUNX3. We found that LINC00657 overexpression promoted the cytotoxic activity of NK cells via regulating RUNX3/DR5 axis. Therefore, LINC00657 suppressed cervical cancer progression via inducing miR-20a-5p/RUNX3/DR5 mediated NK cell tolerance. In conclusion, LINC00657 was identified as a novel tumor-suppressor in cervical cancer and could function as a potential therapeutic target for clinical treatment.

Abstract 2517: Ectopic expression of miR-142-3p suppresses growth, migration, colony formation and induces apoptosis by down-regulating HMGA1, HMGA2, HMGB1 and HMGB3 in human cervical cancer cells

Abstract High Mobility Group (HMG) proteins are non-histone chromosomal proteins having molecular weight less than 30 kDa. Canonical HMG family of proteins include HMGA (A1 and A2), HMGB (B1, B2, B3, and B4) and HMGN (N1, N2, N3, N4 and N5). Overexpression of HMG proteins contributing to their oncogenic properties has been reported and thus inhibition of their expression is potentially a promising therapeutic strategy in different cancers. Earlier, our laboratory demonstrated that miR-214 downregulates HMGA1 and miR-34a downregulates HMGB1 leading to the suppression of growth, proliferative and invasive properties of human cervical and colorectal cancer cells. Prompted by these results, we tried to find a single miRNA which can target multiple HMG genes. To this end, TargetScan, miRWalk, and miRDB were used to find out miRNAs targeting more than one HMG gene. We found that miR-142-3p has its seed region binding sites in the 3'UTRs of HMGA1, HMGA2, HMGB1, and HMGB3. Survival analysis with OncoLnc server revealed that low miR-142-3p expression found in cervical cancer patients correlates with their poor survival. Strengthened by this classical miRNA-target inverse relationship, we hypothesized that miRNA-142-3p may act as a tumor suppressor by targeting multiple HMG genes in cervical cancer. Doxycycline-responsive miR-142-3p expression constructs were used to generate stable cell lines and functional assays were performed. Through dual-luciferase reporter assays, we demonstrate that all the four HMG genes are direct targets of miR-142-3p in four cervical cancer cell lines (HeLa, SiHa, C33A, and CaSki). We observed the downregulation of the HMG genes (through qRT-PCR) upon miR-142-3p overexpression in the stable cell lines. Also, a significant reduction in cell viability after 72 and 96 hours concurrent with the highest expression levels of miR-142-3p. In colony formation assay, colony-forming potential of the cell lines was found to be severely compromised upon miR-142-3p overexpression. The scratch assay was also performed and a slower rate of migration was observed in miR-142-3p overexpressing cells. Annexin V staining indicated that miR-142-3p induces cell death via apoptosis. These results suggest that miR-142-3p may act as a tumor suppressor in cervical cancer highlighting it as a potential candidate for miRNA replacement therapy. Citation Format: Priyanshu Sharma, Poonam Yadav, Devarajan Karunagaran. Ectopic expression of miR-142-3p suppresses growth, migration, colony formation and induces apoptosis by down-regulating HMGA1, HMGA2, HMGB1 and HMGB3 in human cervical cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2517.

Functional characterization of the long noncoding RNA MIR22HG as a tumour suppressor in cervical cancer by targeting IGF2BP2.

Cervical cancer is the most common malignant tumour in the female reproductive tract, ranking second in the global cause of female cancer and seriously endangering women's health. However, the underlying mechanisms leading to cervical cancer are unclear. Previous studies have reported the roles and general underlying mechanisms of the long noncoding RNA MIR22HG (MIR22HG) in multiple types of tumours. In this study, we describe the functional role of MIR22HG as a tumour suppressor lincRNA by regulating metastasis, growth and invasion by performing a series of in vivo and in vitro experiments. Our data suggested that MIR22HG dramatically promoted cervical cancer apoptosis and inhibited invasion by targeting IGF2BP2. The long noncoding RNA MIR22HG targets IGF2BP2 as a tumour suppressor in cervical cancer. Our findings will be helpful for developing potential therapeutics for cervical cancer.

MiR-106a Regulates Cell Proliferation and Autophagy by Targeting LKB1 in HPV-16-Associated Cervical Cancer.

miR-106a is aberrantly regulated in various tumors and plays an important role in carcinogenesis. However, the biological role and molecular mechanism by which miR-106a contributes to cervical squamous cell carcinoma (CSCC) remains elusive. In this study, we verified that miR-106a was elevated in both human papilloma virus (HPV) 16-positive CSCC tissues and cell lines. ROC curve analysis showed that miR-106a could well distinguish HPV-16-positive CSCC tissues from normal cervical squamous epithelium tissues. High expression of miR-106a was associated with malignant clinicopathologic parameters in CSCC tissues. Exogenous expression of miR-106a greatly promoted cervical cancer cell proliferation while attenuated autophagy. Furthermore, a novel target of miR-106a, liver kinase B1 (LKB1), a proven tumor suppressor in cervical cancer was verified. Here we confirmed LKB1 was negatively correlated with malignant clinicopathologic parameters in CSCC tissues. Overexpression of LKB1 neutralized the effect of miR-106a on proliferation and autophagy in cervical cancer cell lines. In addition, the role of miR-106a in cell proliferation and autophagy was via LKB1 and its downstream pathway AMP-activated protein kinase-mammalian target of rapamycin. Of note, miR-106a was upregulated by HPV-16 E7 protein. The function of HPV-16 E7 to cell proliferation was suppressed when knockdown miR-106a in HPV-16 E7-expressing cells. IMPLICATIONS: Our study highlights the tumorigenic role and regulatory mechanism of miR-106a in CSCC. miR-106a may be a potential therapeutic target in HPV-associated cervical cancer.