<p>Effects of miR-384 and miR-134-5p Acting on YY1 Signaling Transduction on Biological Function of Gastric Cancer Cells</p>

Abstract

Objective: To explore the related influencing mechanism of miR-384 and miR-134-5p acting on Yin Yang 1 (YY1) signaling transduction on the biological function of gastric cancer (GC) cells. Methods: miR-384, miR-134-5p and YY1 levels in human GC cell lines KATO III, MKN-45, SNU-1 and normal gastric cell line GES-1 were measured by polymerase chain reaction (PCR). Dual luciferase reporter (DLR) gene assay and Western blot (WB) were employed for correlation analysis between miR-384, miR-134-5p and YY1. miR-384-inhibitor, miR-384mimics, empty plasmid (miRNA-NC) and sh-YY1 were transfected into KATO III cells. Cell proliferation was determined by 3-(4,5-Dimethylthiazolyl-2)-2,5-Diphenyl Tetrazolium Bromide (MTT), cell invasion was measured by Transwell, and apoptosis was analyzed by flow cytometry (FC). Results: In KATO III, MKN-45 and SNU-1 cell lines, YY1 was upregulated while miR-384 and miR-134-5p were downregulated (P<0.001). The expression of miR-134-5p in the miR-134-5p-inhibitor group was significantly lower (P<0.001), while that in the miR-134-5pmimics group was significantly higher (P<0.001). The expression of miR-384 in the miR-384-inhibitor group was significantly lower (P<0.001), and that in the miR-384-mimics group was significantly higher as compared to the NC group (P<0.001). Both miR-384 and miR-134-5p overexpression could inhibit cell proliferation and invasion, and promote apoptosis. As detected by WB, overexpressed miR-384 and miR-134-5p inhibited the expression of EMT-related molecular markers. Compared with sh-YY1, the number of cells in S phase decreased, the pro-apoptotic proteins boosted statistically, and the anti-apoptotic proteins declined notably after transfecting miR-134-5p-mimics/sh-YY1 or miR-384-mimics/sh-YY1 (P<0.05). The tumor growth rate of nude mice in miR-134-5p/sh-YY1 and miR-384/sh-YY1 groups were significantly lower than those in sh-YY1 group (all P<0.001). Conclusion: By targeting YY1 signaling transduction, miR-134-5p and miR-384 can alter the growth and apoptosis of GC cells, which are promising targets for new therapeutics of GC.

Circ_0037866 Contributes to the Tumorigenesis of Renal Cell Carcinoma by Sequestering miR-384 to Elevate Chromobox 5 Expression

“…Besides, circ_0037866 could indirectly regulate CBX5 expression via interacting with miR-384 in RCC cells. MiR-384 is a well-recognized tumor suppressor in many cancers [26,27]. In RCC, it was also demonstrated to suppress cell growth and motility [28][29][30], and the same results were also observed in this work.…”

Luteolin attenuates the chemoresistance of osteosarcoma through inhibiting the PTN/β-catenin/MDR1 signaling axis by upregulating miR-384

“…In our research, PTN was identified as a direct target of miR-384 by the bioinformatic analysis, dual luciferase reporter assay, gain-of-function and loss of-function assays, which coincided with the study conducted by Yao et al [20] Recent studies indicated that miR-384 acts as a tumor suppressor in several types of human malignant tumors. It could inhibit cell viability, invasion, migration and promote apoptosis in many tumors such as gastric cancer, colorectal cancer, non-small cell lung cancer, nasopharyngeal carcinoma, glioma, papillary thyroid cancer, prostate cancer, pancreatic cancer, et al [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] In osteosarcoma, there is also some evidence that miR-384 could promote apoptosis and exert suppressive effect on cell proliferation, invasion, and migration [24] , [25] , [26] . In our work, we found that miR-384 could enhance the apoptosis induced by doxorubicin or cisplatin in OS cells.…”

Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesis

“…The high expression levels of RSF-1 (part of the RSF complex) were associated with poor prognosis in GC 86 , and knockdown of the NURF complex subunits showed tumor suppressive effects in GC cells, further supporting their roles in GC 87 . While the role of the INO80 complex in gastric carcinogenesis is relatively unexplored, it contains YY1 as a subunit 88 , a transcription factor known to activate multiple oncogenic pathways in GC [89][90][91][92][93][94] . However, whether this activation is mediated by INO80 has yet to be elucidated.…”