Pathogenesis Of Cervical Cancer Research Articles

Melatonin: A new inhibitor agent for cervical cancer treatment.

Cervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early stages allows it to be a preventable and generally treatable disease. Increasing evidence revealed, a variety of internal and external factors are associated with initiation and progression of cervical cancer pathogenesis. Human papilloma virus infection is found as a major cause of cervical cancer. Other molecular and biochemical alterations as well as genetic and epigenetic changes are related cervical cancer progression. Current treatment options often have severe side effects and toxicities thus, new adjuvant agents having synergistic effects and ability to decrease different side effects and toxicities are needed. Melatonin is an indolamine compound secreted from the pineal gland which shows wide range anticancer activities. A large amount of studies indicated inhibitory effects of melatonin against various types of cancers. In addition, experimental evidence reports inhibitory effects of melatonin as an adjuvant therapy on cervical cancer by targeting a sequence of different molecular mechanisms. Herein, for first time, we summarized anticervical cancer effects of melatonin and its underlying molecular mechanisms.

TIPE1 Inhibits Breast Cancer Proliferation by Downregulating ERK Phosphorylation and Predicts a Favorable Prognosis.

TIPE1, which acts as a cell death regulator, has emerged as a tumor suppressor in the process of carcinogenesis. However, our recent research demonstrated that it serves as an oncogene in the pathogenesis of cervical cancer, indicating that the role of TIPE1 in carcinogenesis needs to be further evaluated. In this study, we show that TIPE1 is able to inhibit breast cancer cell growth both in vivo and in vitro. Functionally, TIPE1 inhibits cancer cell proliferation preferentially by downregulating ERK phosphorylation. Furthermore, the expression of TIPE1 is decreased in breast cancer tissues compared to matched adjacent tissues, and its expression is positively correlated with patients' lifespan. These data indicate that TIPE1 suppresses breast cancer proliferation by inhibiting the ERK signaling pathway. This study also suggests that TIPE1 could serve as a potential therapeutic target and a diagnostic biomarker for breast cancer.

Association of forkhead box protein O1 and paired box gene 3 overexpression with prognosis in patients with cervical cancer.

e14519 Background: Transcriptional factor FOXO1and PAX3 has been reported to play an imported role in human cancer, but the role in cervical cancer has not yet been clarified. Here, we evaluated the functional role of FOXO1 with cervical cancer cells and the expression together with clinical significance of FOXO1 and PAX3 among cervical lesions was investigated. Methods: In vitro assessment of cell functions by cell viably assay, cell migration and invasion assay was evaluated using FOXO1 knockdown cervical cancer cell lines. Immuno-histochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with tissue microarray (TMA) consisting of 209 cervical cancers, 366 high grade cervical intraepithelial neoplasias (CIN), 130 low grade CIN and 328 matched nonadjacent normal cervical epithelial tissues. The clinical significance was investigated by comparing the data with various clinicopathologic characteristics, including survival in cervical cancer. Results: In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability ( p< 0.001), migration ( p< 0.001) and invasion ( p< 0.05) supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p< 0.001) and cancer tissue (both p< 0.001) than in normal tissue. FOXO1 expression showed significant correlation with PAX3 (Spearman’s rho = 0.377, p< 0.001) in a cervical cancer. Multivariate analysis indicates that FOXO1 expression (hazard ratio = 4.01 [95% CI, 1.22–13.10], p= 0.021) and advanced FIGO stage (hazard ratio = 3.89 [95% CI, 1.35–11.19], p= 0.012) were independent prognostic factor on overall survival. Conclusions: This study reveals the association between FOXO1 and PAX3 expression with clinicopathologic variables, including survival of cervical cancer patients. Our results not only suggest the promising potential of FOXO1 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and the pathogenesis of cervical cancer.

LncRNA NOC2L-4.1 functions as a tumor oncogene in cervical cancer progression by regulating the miR-630/YAP1 pathway.

Long noncoding RNA (lncRNA) is a new class of noncoding RNA playing an indispensable role in different diseases by regulating miRNA. Our previous studies have suggested that miR-630 was decreased in patients withcervical cancer. Recently, studies have shown that lncRNA NOC2L-4.1 was abnormally expressed in patients withcervical cancer and can target miR-630. Therefore, we wanted to identify the integrated relationship between lncRNA NOC2L-4.1 and miR-630 in the pathological processes regarding cervical cancer either in vitro or in vivo. Quantitative reverse transcription-polymerase chain reaction detection shows that compared with human normal cervical epithelial cell, the expression of lncRNA NOC2L-4.1 was significantly increased and the expression of miR-630 was decreased in cell lines of cervical cancer. Moreover, luciferase reporter assay showed that miR-630 was a target of lncRNA NOC2L-4.1. The in vitro study found that downregulation of lncRNA NOC2L-4.1 suppressed cervical cancer cell migration (transwell assays) and proliferation (cell counting kit-8 and cloning formation assays). miR-630 specific inhibitor treatment reversed the inhibitory effect of lncRNA NOC2L-4.1 on cell proliferation and migration. Further studies also found that yes-associated protein 1 (YAP1) was the target of miR-630. Overexpression YAP1 suppressed miR-630 overexpression induced cell proliferation and inhibition of migration. Tumors induced by implantation of lncRNA NOC2L-4.1-knockdown Hela cells in nude mice showed that lncRNA NOC2L-4.1 silencing decreased the growth of tumors in both volume and weight by regulation of miR-630/YAP1. Taken together, our study reveals the important role of lncRNA NOC2L-4.1/miR-630/YAP1 regulatory network in cervical cancer, which provides new insights concerning the pathogenesis of cervical cancer.

Systematic Profiling and Evaluation of Structure-based Kinase–Inhibitor Interactome in Cervical Cancer by Integrating In Silico Analyses and In Vitro Assays at Molecular and Cellular Levels

Various protein kinases are implicated in the pathogenesis of human cervical cancer and many kinase inhibitors have been used to regulate the activity of protein kinases involved in the disease signaling networks. In the present study, a systematic kinase–inhibitor interactome is created for various small-molecule inhibitors across diverse cervical cancer-related kinases by using ontology enrichment, molecular docking, dynamics simulation and energetics analysis. The interactome profile is examined in detail with heatmap analysis and heuristic clustering to derive promising inhibitors that are highly potential to target the kinome of human cervical cancer in a multi-target manner. A number of hit and unhit inhibitors are selected and their cell-suppressing effects are tested against human cervical carcinoma HeLa, from which several inhibitor compounds with high cytotoxicity are successfully identified. A further kinase assay confirms that these inhibitors can generally target their noncognate kinases HER3 and BRaf in cervical cancer with a high or moderate activity; the activity profile are comparable with or even better than that of cognate kinases inhibitors, with IC50 values ranging between 4.8 and 340.6 nM for HER3 and between 37.2 and 638.2 nM for BRaf. This work would help to identify those unexpected kinase–inhibitor interactions in human cervical cancer and to develop new and efficient therapeutic strategy combating the disease.

Circ-ATP8A2 promotes cell proliferation and invasion as a ceRNA to target EGFR by sponging miR-433 in cervical cancer

Cervical cancer (CC), a common gynecological carcinoma, is a serious threat to women's health. The dysregulation of circular RNAs (circRNAs) is associated with the pathogenesis of cervical cancer. Therefore, we explored the role of circ-ATP8A2 in CC cell development and progression. Circ-ATP8A2 profiles in CC specimens and cells were detected using real-time PCR. In addition, cell counting kit-8 (CCK-8), acridine orange/ethidium bromide (AO/EB), flow cytometric, and Transwell experiments were carried out on HeLa and SW756 cells to determine cell proliferation, apoptosis, migration and invasion. Furthermore, the mechanism of circ-ATP8A2 was explored by dual-luciferase reporter system. Circ-ATP8A2 was significantly enhanced in CC specimens and cells. Knockdown of circ-ATP8A2 inhibited cell proliferation, migratory and invasive capacities and increased apoptotic cells. Ectopically expressed circ-ATP8A2 induced the opposite effects. For the mechanism exploration, circ-ATP8A2 sponges miR-433 to release its suppression on epidermal growth factor receptor (EGFR) expression at post-transcriptional level. What's more, circ-ATP8A2 could promote cell progression by miR-433/EGFR axis in CC cells. Collectively, this work might offer a potential treatment target for CC. AbbreviationsUnlabelled TableAO/EBacridine orange/ethidium bromideCCcervical cancerCCK-8cell counting kit-8circRNAscircular RNAsEGFRepidermal growth factor receptorPIpropidium iodide

MiR-144-3p: a novel tumor suppressor targeting MAPK6 in cervical cancer.

Cervical cancer is the third most common gynecologic cancer in the world. Exploration of the molecular mechanism underlying cervical cancer pathogenesis will provide new insights into the development of novel therapies. In this study, we were aimed to characterize a novel miRNA in cervical cancer tumorigenesis. First, we measured the expressional change of miR-144-3p in clinical tissues and cancer cells. Second, we employed cell proliferation, cell migration, and invasion assays to understand its functional role in cervical cancer. Then, we confirmed in vitro findings in xenograft cancer model. Last, we mapped out a downstream target of miR-144-3p and validated its functional role in cancer cells. In the results, miR-144-3p was found significantly downregulated in cervical cancer cells and tissues. Over-expressing miR-144-3p suppressed cancer cells growth and metastasis. Consistent with in vitro results, over-expressing miR-144-3p led to tumor growth inhibition in vivo. Further on, MAPK6 was identified as an endogenous target of miR-144-3p in cervical cancer. Knocking down MAPK6 inhibited cervical cancer cells proliferation, migration, and invasion potential. Our investigation was the first time to report miR-144-3p as a tumor suppressive miRNA in cervical cancer. It inhibited tumor growth by targeting MAKP6. The newly identified signalling axis may serve as novel therapeutic targets to manage cervical cancer.

Involvement of NEAT1/miR-133a axis in promoting cervical cancer progression via targeting SOX4.

NEAT1 is an important tumor oncogenic gene in various tumors. Nevertheless, its involvement remains poorly studied in cervical cancer. Our study explored the functional mechanism of NEAT1 in cervical cancer. NEAT1 level in several cervical cancer cells was quantified and we found NEAT1 was greatly upregulated in vitro. NEAT1 knockdown inhibited cervical cancer development through repressing cell proliferation, colony formation, capacity of migration, and invasion and also inducing the apoptosis. For another, microRNA (miR)-133a was downregulated in cervical cancer cells and NEAT1 negatively modulated miR-133a expression. Subsequently, we validated that miR-133a functioned as a potential target of NEAT1. Meanwhile, SOX4 is abnormally expressed in various cancers. SOX4 was able to act as a downstream target of miR-133a and silencing of SOX4 can restrain cervical cancer progression. In addition, in vivo assays were conducted to prove the role of NEAT1/miR-133a/SOX4 axis in cervical cancer. These findings implied that NEAT1 served as a competing endogenous RNA to sponge miR-133a and regulate SOX4 in cervical cancer pathogenesis. To sum up, it was implied that NEAT1/miR-133a/SOX4 axis was involved in cervical cancer development.

TNF-α-induced lncRNA LOC105374902 promotes the malignant behavior of cervical cancer cells by acting as a sponge of miR-1285-3p

Long noncoding RNAs (lncRNAs) regulate gene expression at epigenetic, transcriptional, post-transcriptional levels and play important roles in tumorigenesis and inflammation. In order to explore the effects of lncRNAs on the malignant behavior of cervical cancer (CC) which may be involved in mechanism stimulated by inflammatory factors, we screened a differential expression profile of lncRNAs in CC cells stimulated by TNF-α by deep sequencing. We characterized a significantly upregulated lncRNA LOC105374902 induced by TNF-α. Then, we found that TNF-α accelerated the binding of STAT3 to the promoter region of lncRNA LOC105374902 and promoted its expression. Mechanistically, lncRNA LOC105374902 directly bond to miR-1285-3p as a competing endogenous RNA (ceRNA) to derepress RPL14; functional analysis indicated that both lncRNA LOC105374902 and RPL14 promoted migration, invasion and epithelial-mesenchymal transition (EMT) of CC cells. Taken together, TNF-α-induced lncRNA LOC105374902 may function as a ceRNA for miR-1285-3p to promote the expression of RPL14, promoting the migration, invasion and EMT of CC cells. These findings may provide new insights into the molecular pathogenesis of CC.

CDK6 3'UTR polymorphisms alter the susceptibility to cervical cancer among Uyghur females.

AimsCyclin dependent kinase 6 (CDK6) plays a crucial role in malignant tumor whereas less is reported in cervical cancer development. The aim of this study was to evaluate the effects of CDK6 3' untranslated region (3'UTR) polymorphisms on cervical cancer susceptibility among Uyghur females.MethodsThe genotypes of the six CDK6 variants (rs8179, rs42032, rs42033, rs42034, rs42035, and rs42038) were identified among 306 cervical cancer cases and 310 healthy controls with the Agena MassARRAY platform. The associations of the candidate single nucleotide polymorphisms (SNPs) with the cervical cancer risk were evaluated under genetic models using conditional logistic regression analysis. Bioinformatics analysis was performed for SNP function prediction with the online databases. The expression differences between tumor tissues and normal cervix samples were also examined by Real‐time PCR.Results CDK6 rs8179 and rs42033 were correlated to the decreased risk of cervical cancer in Uyghurs under the allele model (rs8179 and rs42033: OR = 0.60, 95% CI: 0.37–0.99, p = 0.043) and log‐additive model (rs8179 and rs42033: OR = 0.62, 95% CI: 0.38–1.00, p = 0.047). Rs8179, rs42032, and rs42033 were associated with susceptibility to high‐grade cervical cancer in different genetic models as well (p < 0.05). Dataset‐based analysis also uncovered the potential effects of these significant SNPs. In addition, aberrant expression of CDK6 were detected in cervical tumors.ConclusionsOur results suggested the relationships between CDK6 3'UTR polymorphisms and cervical cancer pathogenesis, and the involvement of CDK6 in cervical cancer development among Uyghur females.

Ribociclib, a selective cyclin D kinase 4/6 inhibitor, inhibits proliferation and induces apoptosis of human cervical cancer in vitro and in vivo

Cervical cancer remains one of the main factors leading to tumor-related death worldwide. Many strategies of cancer treatment such as chemotherapy are developed and used nowadays. However, for the cancer chemotherapy resistance, reduction of the limitation of cancer chemotherapy efficacy is one of the aims of several oncology teams. Moreover, the cyclin-dependent kinase 4/6-cyclin D-retinoblastoma protein-E2F pathway is an important mechanism for cell cycle control and its dysregulation is one of the key factors for cancers development including cervical cancer. Ribociclib is one of the selective CDK4/6 inhibitors and is a new therapeutic approach showing promise as a good strategy of therapy in many human cancers. However, there are not the studies regarding the investigation of effects of Ribociclib in cervical cancer yet. In the present study, by western blotting and immunofluorescence assay, we found respectively that CDK4, CDK6 and cyclin D1 are highly expressed and are mostly localized in the nucleus with some localized in the cytoplasm of cervical cancer cell lines. Moreover, Ribociclib induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited C33A cell proliferation in dose – dependent manner following by decreased expression of certain related genes such as CDK4, CDK6, E2F1, P-Rb, and increased Bax expression. In C33A xenografts, Ribociclib inhibited tumor growth associated with decreased expressions of CDK4, CDK6, cyclin D1, Rb and Ki-67, and also significantly increased tumor cell apoptosis. However, we didn’t find side effect of Ribociclib concerning heart, liver and kidney perturbation and any Ribociclib anti-tumor effects on HeLa in vitro and in vivo which may be due to Hela cell infection by HPV. Based on our findings, the Rb-E2F pathway can be considered as an important factor in human cervical cancer pathogenesis and as a mechanism of Ribociclib, a potential strategy of treatment for the improvement of new therapeutic measures for the treatment of HPV-negative cervical cancer which application for HPV-positive cervical cancer is desired in further study.

Protective Effects of Downregulating Estrogen Receptor Alpha Expression in Cervical Cancer.

The cause of cervical cancer can be traced to Human Papilloma Virus (HPV) along with other, nonviral factors. The uterine cervix is reactive to hormones, and female hormones have been implicated in cervical cancer pathogenesis. Previous studies have indicated that malignant cervical cells tend to lose Estrogen Receptor alpha (ER-α) expression in the cervical epithelium while maintaining ER-α expression in the stromal cells. We searched the Web of Science, Embase, PubMed, and Wiley Online Library databases to identify potentially relevant articles up to July 4, 2018. Keywords include uterine cervical neoplasms; receptors, estrogen; estrogen receptor alpha; estrogen receptor modulators; estrogens; cervical cancer and estrogen receptor. Discussions on molecular transitions and drug therapies offer insights into cervical cancer and the functions of estrogen receptors. We focus on molecular transitions and drug therapies for cervical cancer and ER-α targets. Finally, the targeting of downstream gene products and/or receptors to aid in cervical cancer prevention and therapy is discussed. Downregulating ER-α expression may be a potential treatment regimen for cervical cancer patients and will be of great significance for patients with cervical cancer who are receiving conventional treatment for nonsurgical treatments.

Overexpression of chloride channel-3 (ClC-3) is associated with human cervical carcinoma development and prognosis

BackgroundCervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research. ClC-3 may be an important promoter for aggressive metastasis of malignant tumors. In this research, we explore the ClC-3 expression in cervical carcinoma and its underlying clinical significance, trying to illuminate ClC-3 probable function in the neoplasm malignant behavior, development and prognosis.MethodsParaffin-embedded cervical (n = 168) and lymph node (n = 100) tissue specimens were analysed by immunohistochemistry. Fresh human cervical tissue specimens (n = 165) and four human cervical cell lines were tested for ClC-3 mRNA and protein expression levels by quantitative real-time PCR and western blotting. The relationship between the expression levels of ClC-3, the pathological characteristics of the carcinoma, and the clinical prognosis were statistically analysed.ResultsIn normal and precancerous (LSIL, HSIL) cervical tissues as well as cervical carcinoma tissues, both ClC-3 mRNA and protein expression levels increased significantly (p < 0.05). The expression level of ClC-3 was closely-related to the histological differentiation (p = 0.029), tumour staging (p = 0.016), tumour size (p = 0.039), vascular invasion (p = 0.045), interstitial infiltration depth (p = 0.012), lymphatic metastasis (p = 0.036), and HPV infection (p = 0.022). In an in vitro experiment, ClC-3 mRNA and protein were found to be overexpressed both in the HeLa and SiHa cell lines, but low expression levels were detected in the C-33A and H8 cell lines (p < 0.05). Furthermore, the high expression levels of ClC-3 was significantly correlated to poor survival in cervical carcinoma patients (Log-rank test, p = 0.046).ConclusionsThese data suggest that overexpression of ClC-3 is closely associated with human cervical carcinoma progression and poor prognosis; this suggests that ClC-3 may function as a patent tumour biomarker and a latent therapeutic target for cervical carcinoma patients.

Overexpression of LINC00037 represses cervical cancer progression by activating mTOR signaling pathway.

Long non-coding RNAs have been reported to play crucial roles in tumorigenesis including cervical cancer. LINC00037 has been identified as a significant regulator in several cancers. Our study was aimed to investigate the function of LINC00037 in cervical cancer progression. LINC00037 was significantly downregulated in human cervical cancer cells (HeLa, HCC94, HT-3, Caski, and SiHa cells) compared with the ectocervical epithelial cells (End1/E6E7 cells). Overexpression of LINC00037 was able to inhibit cervical cancer cell proliferation, induce cell apoptosis, and restrain the cell migration/invasion capacity. Reversely, knockdown of LINC00037 exhibited an opposite process in vitro. mTOR has been recognized as an atypical serine/threonine kinase that is involved in regulating significant cellular functions. In our present study, we observed that the mTOR signaling pathway was strongly activated in human cervical cancer cells. Meanwhile, upregulation of LINC00037 contributed to the inactivation of mTOR signaling whereas downregulation of LINC00037 activated the pathway. Subsequently, in vivo animal models using SiHa cells were established and we proved that LINC00037 repressed cervical cancer progression via targeting the mTOR signaling pathway. All these findings implied that LINC00037 could regulate cervical cancer pathogenesis via mTOR signaling. In conclusion, a novel role of LINC00037 was manifested in cervical cancer progression.

Mathematical model for predicting the risk of progression of cervical dysplasia associated with papillomavirus infection in women with infertility.

Background. During recent decades there has been a new concept of the pathogenesis of cervical cancer, according to which dysplasia of the cervix (CIN) of CIN1 is an inflammatory process with the development of pathological regeneration that corresponds to productive papillomavirus infection and, more often, may be reversible. Morphological manifestations of moderate to severe dysplasia of the cervix are discussed in the context of neoplasia. Objective. The determination of the predictor factors and create a mathematical model for predicting the risk of progression of cervical dysplasia associated with papillomavirus infection in women with infertility. Methods. The construction of the mathematical model, regression analysis, and the values of the coefficients of multiple regression were determined using the SPSS program. Results. To determine the risk of HPVI-associated CIN progression the mathematical model was created: RP CINI=0,011*Ki-67-0,011* NKSSE/CBD +0,009*p63+0,018*age+0,032*infertility form-0,075*infertility type-0,014*duration of infertility+1,481 (constant), where, Кі-67 –the level of expression of the marker of cell proliferation, %; р63 –the level of expression of the protooncogene, %; NKSSE/CBD – height index of non-keratinized stratified squamous epithelium (NKSSE) to a capillaries bulk density (CBD); an age: number of years of the patient; infertility form: 1 – hormonal, 2 – pipe, 3 – peritoneal, 4 – combined; infertility type: 1 – primary, 2 – secondary; a duration of infertility: number of years. Individual value RP CIN is interpreted according to the differential values of the split points: [0; 1,5] – low risk of progression; [1,5; 2,5], risk of moderate CIN progression; [2,5; 3] – risk of severe CIN progression. Conclusion. The proposed program and algorithm of mathematical modeling allows us to verify the degree of severity, to calculate the digital level of progression of CIN associated with PVI in women with infertility, to form groups of clinical supervision, to choose the strategy of adequate medical tactics and to timely apply preventive methods against the progress of this disease.

Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p.

Circular RNA (circRNA) is a new class of noncoding RNA, and plays an important role in many pathological processes. Cervical cancer is the most common gynecologic malignant tumor. Recently, studies have shown that there is a variety of circRNA involved in the pathogenesis of cervical cancer. We screened out the highly expressed hsa_circ_0000263 from GSE102686 by the quantitative real-time polymerase chain reaction assay in cervical cancer cell lines. In this study, we investigated whether hsa_circ_0000263 might affect cell proliferation, migration, cell cycle and apoptosis in cervical cancer in vitro and in vivo. The luciferase reporter assay and RNA immunoprecipitation assay confirmed the direct interaction between miR-150-5p and hsa_circ_0000263. By using western blot and immunohistochemistry, we confirmed that hsa_circ_0000263 can regulate the expression of murine double minute 4 (MDM4) by affecting miR-150-5p, and finally affect the expression of p53 gene. We found that hsa_circ_0000263 was significantly upregulated in cervical cancer cells. In addition, the knockdown of hsa_circ_0000263, would inhibit cell proliferation and migration ability. In conclusion, our current research reveals the important role of hsa_circ_0000263/miR-150-5p/MDM4/p53 regulatory network in cervical cancer and provides a new insight into the pathogenesis of cervical cancer.

Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning

BackgroundTo better understand the pathogenesis of cervical cancer (CC), we systematically analysed the genomic variation and human papillomavirus (HPV) integration profiles of cervical intraepithelial neoplasia (CIN) and CC.MethodsWe performed whole-genome...

Long Non-Cod-ing RNA Signature in Cervical Cancer.

Cervical cancer as acommon urogenital cancer among women has caused significant health problems. Efforts have been made to identify its pathogenic process in order to find targeted ther-apies. Long non-cod-ing ribonucleic acids (lncRNAs) have been shown to regulate several cancer-related pathways and genes that contribute to pathogenesis of human malignancies, includ-ing cervical cancer. In the present review, we searched PubMed, Google scholar, Web of Science and Scopus databases for key words "cervical cancer" or "cervical neoplasm" and "long non-cod-ing RNA" or "lncRNA" (up to December 2017). To elaborate the role of lncRNAs in cervical cancer. LncRNAs affect cervical cancer pathogenesis through numerous mechanisms, such as mak-ing scaffolds for assembly of protein complexes, serv-ing as directors to recruit proteins, function-ing as transcriptional enhancers through chromatin remodeling, serv-ing as decoys to free up proteins from chromatin, or revers-ing the effects of other regulatory non-cod-ing RNAs, such as microRNAs. Pathway-based analysis showed that several lncRNAs modulate PI3K/ Akt/ mTOR, Wnt-β catenin and Notch pathways in the process of cervical cancer pathogenesis. In addition, expression of ahandful of lncRNAs has been associated with human papilloma virus infection. Identification of lncRNAs that alter cancer-related signal-ing pathways and subsequent expression analysis of these lncRNAs in patients samples would help to design effective targeted ther-apies. Key words: lncRNA- cervical cancer - oncogene - tumor suppressor gene.

Overexpression of MALAT1 contributes to cervical cancer progression by acting as a sponge of miR-429.

Cervical cancer remains a malignant type of tumor and is the fourth leading cause of cancer-related death among females. MALAT1 has been identified as a tumor oncogene in various cancers. Our present study aimed to explore the biological role of MALAT1 in cervical cancer. We observed that MALAT1 was significantly upregulated in human cervical cancer cell lines compared with the ectocervical epithelial cells. MALAT1 was repressed by transfection with LV-shMALAT1, whereas increased by LV-MALAT1 in HeLa and Caski cells. Silencing of MALAT1 obviously reduced cervical cell viability, induced cell apoptosis, and repressed cell invasion capacity. Conversely, overexpression of MALAT1 exhibited an opposite phenomenon. Furthermore, miR-429 was predicted as a direct target of MALAT1, and it was dramatically decreased in cervical cancer cells. It has been shown that miR-429 plays a crucial role in cervical cancer progression. In our current study, the targeting correlation between MALAT1 and miR-429 was confirmed by luciferase reporter assays and RIP experiments. Finally, in vivo animal models were established, and we indicated that MALAT1 inhibited cervical cancer progression via targeting miR-429. These findings revealed that MALAT1 can sponge miR-429 and regulate cervical cancer pathogenesis in vivo and in vitro. In conclusion, we indicated that the MALAT1/miR-429 axis was involved in cervical cancer development.

Oxidative stress in cervical cancer pathogenesis and resistance to therapy.

Cervical cancer (CC) is one of the most common cancers among females, and it is most notable in developing countries. The exact etiology of CC is poorly understood; but, smoking, oral contraceptives, immunosuppression, and infection with human papillomavirus (HPV) may increase the risk of CC. There is also an association between CC and oxidative stress. Oxidative stress is caused by a disturbed oxidant-antioxidant balance in favor of the former, leading to an excessive generation of free radicals, particularly reactive oxygen species (ROS), and subsequently to biological damages. Thus, redox enzymatic and nonenzymatic regulators are required to maintain the redox homeostasis. Dysregulated antioxidants system and the pathogenic role of oxidative stress in CC have been investigated in several clinical and preclinical studies. In this study, we reviewed studies that have addressed the cross-talk between oxidative stress and CC pathogenesis and resistance to therapy.