Rui Tong

LILRB4 shapes an immunosuppressive microenvironment to drive cervical cancer progression through tumor-infiltrating myeloid cell expansion and CD8+ T-cell suppression

Cervical cancer (CC) is the most common gynecological malignancy and is strongly linked to human papillomavirus (HPV) infection. Currently, immune checkpoint blockade therapy has shown limited clinical benefits for CC, highlighting the need to find more effective therapeutic targets. LILRB4, a member of the leukocyte immunoglobulin-like receptor superfamily, is considered a key mediator of cancer immunosuppression. However, its role in the CC immune microenvironment remains unclear. Here, LILRB4 expression was upregulated in CC tissues, and high expression levels were positively associated with advanced disease and immunosuppressive genes in tumors. In an immunocompetent mouse model, LILRB4 expression in CC tumors increased with tumor growth, whereas blocking LILRB4 reduced tumor growth. Flow cytometry analysis revealed that blockade of LILRB4 reduced CD8

Inhibition of miR-574-5p suppresses cell growth and metastasis and enhances chemosensitivity by targeting RNA binding protein QKI in cervical cancer cells

Cervical cancer is the fourth most common female malignancy worldwide and microRNA (miR)-574-5p is a candidate oncogene in multiple cancers. The present study aimed to investigate the role and mechanism of miR-574-5p in cervical cancer. miR-574-5p inhibitors or mimics were transfected into cervical cancer cells to study the function of miR-574-5p. The effects of miR-574-5p on cell growth, invasion, and chemosensitivity were evaluated using CCK8, flow cytometry, transwell, immunofluorescence, and Western blotting analysis. Further depletion or forced expression of QKI was performed to explore the regulatory mechanism of miR-574-5p in cervical cancer. Up-regulation of miR-547-5p and down-regulation of QKI were observed in 30 cervical cancer tissues versus 30 adjacent normal tissues. Silencing of miR-574-5p increased apoptosis, inhibited proliferation, cell cycle progression, and cell invasiveness, as well as enhanced chemosensitivity towards cisplatin and doxorubicin in cervical cancer cells. Overexpression of miR-574-5p exerted promoting effect on cancer progression and metastasis. Knockdown of miR-574-5p induced an up-regulation of E-cadherin and down-regulation of cyclinD1, N-cadherin, matrix metallopeptidase 9 (MMP-9), and β-catenin in cervical cancer cells Moreover, QKI was verified as a target of miR-574-5p and involved in regulation of miR-574-5p-induced cervical cancer cell progression and metastasis. miR-574-5p functions to be oncogenic in cervical cancer, and its inhibition suppresses cervical cancer progression and metastasis as well as enhances chemosensitivity by targeting QKI. Therefore, miR-574-5p is suggested as a potential therapeutic target for cervical cancer treatment.

LncRNA PTCSC3 inhibits the proliferation, invasion and migration of cervical cancer cells via sponging miR‐574‐5p

AbstractDysregulation of long non‐coding RNA papillary thyroid carcinoma susceptibility candidate 3 (lncRNA PTCSC3) has been found to correlate with various types of cancers. Quantitative RT‐PCR showed a down‐regulation of PTCSC3 in cervical cancer tissues compared with normal cervical tissues. The present study aimed to investigate the role of lncRNA PTCSC3 in cervical cancer and the underlying mechanisms. PTCSC3 was overexpressed in cervical cancer cell lines C‐33A and Hela by transfection with pcDNA3.1‐lncRNA PTCSC3 expressing plasmid. Overexpression of lncRNA PTCSC3 inhibited cell proliferation, induced cell cycle arrest, and suppressed cell invasion and migration using CCK8 assay, flow cytometry, Transwell assay and wound healing examination, respectively. Western blotting analysis showed that PTCSC3 overexpression decreased the expression of cyclinD1, matrix metalloproteinases 9 (MMP9), N‐cadherin and β‐catenin and increased E‐cadherin expression. Further, PTCSC3 negatively regulated miR‐574‐5p expression and dual‐luciferase assay verified the binding activity between miR‐574‐5p and lncRNA PTCSC3. Enforced up‐regulation of miR‐574‐5p abolished the inhibitory effect of lncRNA PTCSC3 on cervical cancer cell proliferation, invasiveness and mobility. Taken together, lncRNA PTCSC3 inhibited cell growth and metastasis via sponging miR‐574‐5p in cervical cancer. Therefore, we demonstrate the tumour‐suppressive function of lncRNA PTCSC3 in cervical cancer and suggest that PTCSC3 is a potential therapeutic target for cervical cancer.

Circ_0005576 Exerts an Oncogenic Role in Cervical Cancer via miR-1305-Dependent Regulation of PAIP1

AbstractCervical cancer (CC) is a leading cause of high morbidity and mortality in women worldwide. Circular RNAs (circRNAs) are considered to be essential regulators of various cancers, including CC. The purpose of this study was to investigate the role and mechanism of circ_0005576 in CC progression. The levels of circ_0005576, miR-1305, and poly(A)-binding protein-interacting protein 1 (PAIP1) were detected by quantitative real-time PCR (qRT-PCR) or western blot assay. The stability and location of circ_0005576 were determined by ribonuclease R (RNase R) assay and subcellular fractionation distribution assay, respectively. Cell proliferation was evaluated by CCK-8 assay, EDU incorporation assay, and colony formation assay. Cell migration and invasion were assessed by transwell assay. The interactions between miR-1305 and circ_0005576 or PAIP1 were validated by dual-luciferase reporter assay. The protein expression of cyclin D1, vimentin, and matrix metallopeptidase 9 (MMP9) was tested by western blot. Moreover, mice xenograft models were constructed to analyze tumor growth in vivo. Circ_0005576 and PAIP1 were upregulated, while miR-1305 was downregulated in CC tissues and cells. Circ_0005576 was a stable circRNA that was mainly distributed in the cytoplasm of cells. Knockdown of circ_0005576 suppressed the proliferation, migration, and invasion of CC cells, while the silence of miR-1305 facilitated the development of CC cells. Meanwhile, circ_0005576 could sponge miR-1305 to promote PAIP1 expression. Furthermore, PAIP1 overexpression relieved the influence of circ_0005576 silence on the growth of CC cells. Additionally, circ_0005576 silence hindered CC tumor growth in vivo. Circ_0005576 depletion suppressed tumor development in CC by regulating the miR-1305/PAIP1 axis, suggesting that circ_0005576 might be a potential biomarker for CC treatment.