LncRNATCF7 up-regulates DNMT1 mediated by HPV-18 E6 and regulates biological behavior of cervical cancer cells by inhibiting miR-155.

OBJECTIVE This work aimed to study the mechanism of lncRNATCF7 upregulating DNMT1 mediated by HPV-18 E6 and regulating the biological behavior of cervical cancer cells by inhibiting miR-155. PATIENTS AND METHODS HPV-16 E6 enhanced DNMT1 expression in cervical cancer cells, which was detected by Western blotting. The expression of miR-155 in cervical cancer was detected by qPCR, the interaction between TCF-7 and miR-155 by Dual-luciferase reporter gene. The changes in invasion ability of cervical cancer cells and the effect of miR-155 on the invasion ability of cervical cancer cells after inhibiting TCF-7 were detected by the transwell invasion assay, while changes in migration ability of cervical cancer cells and the effect of miR-155 on migration ability of cervical cancer cells after inhibiting TCF-7 were observed by the scratch assay. The effect of inhibiting TCF-7 on the tumor size and volume of cervical cancer was detected by the subcutaneous tumor formation in nude mice. RESULTS E6 expression was significantly inhibited by E6 siRNA. The knockdown of endogenous HPV-16 E6 markedly inhibited the expression of DNMT1; TCF-7 specifically bound to the 3' UTR of miR-155; inhibition of TCF-7 can inhibit invasion and migration of cervical cancer cells; enhanced miR-155 after the inhibition of TCF-7 can promote the invasion and migration of cervical cancer cells; compared with NC group, the tumor volume and weight of TCF-7-siRNA group tumor-bearing was significantly reduced. CONCLUSIONS TCF-7 plays an important role in the development of cervical cancer. TCF-7 can target miR-155 to regulate the invasion and migration of cervical cancer cells.

[1]  Yueming Sun,et al.  Construction of ceRNA networks reveals differences between distal and proximal colon cancers. , 2019, Oncology reports.

[2]  Jing Xu,et al.  Long non-coding RNA TCF7 contributes to the growth and migration of airway smooth muscle cells in asthma through targeting TIMMDC1/Akt axis. , 2019, Biochemical and biophysical research communications.

[3]  V. Tomar,et al.  A Feedback Loop between MicroRNA 155 (miR-155), Programmed Cell Death 4, and Activation Protein 1 Modulates the Expression of miR-155 and Tumorigenesis in Tongue Cancer , 2019, Molecular and Cellular Biology.

[4]  Xiaomeng Xia,et al.  The role of lncRNAs in signaling pathway implicated in CC , 2018, Journal of cellular biochemistry.

[5]  Mary M. Cavanagh,et al.  Functional pathways regulated by microRNA networks in CD8 T‐cell aging , 2018, Aging cell.

[6]  W. Zhang,et al.  MiR-155 promotes the proliferation and migration of breast cancer cells via targeting SOCS1 and MMP16. , 2018, European review for medical and pharmacological sciences.

[7]  M. Rietbergen,et al.  Epidemiologic associations of HPV‐positive oropharyngeal cancer and (pre)cancerous cervical lesions , 2018, International journal of cancer.

[8]  P. Sparén,et al.  An overview of cervical cancer epidemiology and prevention in Scandinavia , 2018, Acta obstetricia et gynecologica Scandinavica.

[9]  A. Hussain,et al.  Genistein Induces Alterations of Epigenetic Modulatory Signatures in Human Cervical Cancer Cells. , 2018, Anti-cancer agents in medicinal chemistry.

[10]  Yue Zhang,et al.  Construction of a ceRNA network reveals potential lncRNA biomarkers in rectal adenocarcinoma , 2018, Oncology reports.

[11]  L. Bruni,et al.  Epidemiology and burden of HPV-related disease. , 2017, Best practice & research. Clinical obstetrics & gynaecology.

[12]  S. Bae,et al.  A higher degree of expression of DNA methyl transferase 1 in cervical cancer is associated with poor survival outcome , 2017, International journal of women's health.

[13]  M. Schiffman.  Cervical cancer screening: Epidemiology as the necessary but not sufficient basis of public health practice. , 2017, Preventive medicine.

[14]  P. Szodoray,et al.  MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome , 2017, PloS one.

[15]  Xavier Castellsagué,et al.  Skin Cancer: Epidemiology, Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches , 2017, Dermatology and Therapy.

[16]  L. Pan,et al.  MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN , 2016, Oncotarget.

[17]  Yuanjia Hu,et al.  TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis , 2016, Oncotarget.

[18]  E. Faghihloo,et al.  Transcriptional Suppression of E-Cadherin by HPV-16 E6 and E7 Oncogenes is Independent of Hypermethylation of E-Cadherin Promoter , 2016 .

[19]  N. Lu,et al.  Expression and Function of miR-155 in Diseases of the Gastrointestinal Tract , 2016, International journal of molecular sciences.

[20]  M. Dowsett,et al.  miR-155 Drives Metabolic Reprogramming of ER+ Breast Cancer Cells Following Long-Term Estrogen Deprivation and Predicts Clinical Response to Aromatase Inhibitors. , 2016, Cancer research.

[21]  A. Sjölander,et al.  Bereavement Is Associated with an Increased Risk of HPV Infection and Cervical Cancer: An Epidemiological Study in Sweden. , 2016, Cancer research.

[22]  W. Jonat,et al.  Vulvar cancer: epidemiology, clinical presentation, and management options , 2015, International journal of women's health.

[23]  Hong-bing Chen,et al.  Investigation of microRNA-155 as a serum diagnostic and prognostic biomarker for colorectal cancer , 2015, Tumor Biology.

[24]  Jian Gao,et al.  MiR‐155 targets TP53INP1 to regulate liver cancer stem cell acquisition and self‐renewal , 2015, FEBS letters.

[25]  Wei-Yu Chen,et al.  MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer , 2014, Oncotarget.

[26]  Domenico Coppola,et al.  MicroRNA-155 Regulates Cell Survival, Growth, and Chemosensitivity by Targeting FOXO3a in Breast Cancer* , 2010, The Journal of Biological Chemistry.

[27]  Hong-mei Wang,et al.  Long non-coding RNA TCF 7 predicts the progression and facilitates the growth and metastasis of colorectal cancer , 2018 .

[28]  Liling Li,et al.  DNA methyltransferase ( DNMTs ) expression in cervical cancer tissues and its relationship with HPV infection and tumor malignancy , 2017 .

[29]  Jinhui Wu,et al.  Long noncoding RNA TCF7 promotes invasiveness and self-renewal of human non-small cell lung cancer cells , 2016, Human Cell.