Up-regulated LINC01234 promotes non-small-cell lung cancer cell metastasis by activating VAV3 and repressing BTG2 expression

Abstract

Background: Long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to non-small-cell lung cancer (NSCLC) metastasis remain poorly understood. Our previous and other studies have revealed the involvement of upregulated LINC01234 in regulating gastric cancer and colon cancer cells proliferation, and we aimed to investigate whether LINC01234 overexpression also contribute to cancer cells metastasis in this study. Methods:We collect the NSCLC tissues and adjacent non-tumor tissues and analyzed expression levels of LINC01234 by quantitative reverse-transcription PCR. LINC01234 were knocked down by using siRNAs or shRNAs, and overexpressed by transfection with overexpression vector; RNA levels of miRNA were downregulated or upregulated with inhibitors or mimics. Transwell assays were used to evaluate cell migration and invasive ability; in vivo metastasis experiments were performed to investigate the effect of LINC01234 on NSCLC cells metastasis. Luciferase reporter, RIP, and ChIP assays were used to determine the regulation of LINC01234 on its targets.Results: LINC01234 expression is increased in NSCLC tissues, and its upregulation is associated with metastasis and shorter survival in NSCLC. Downregulation of LINC01234 impairs cell migration and invasion in vitro, and inhibits cells metastasis in vivo by acting as a competing endogenous RNA for the miR-340-5p and miR-27b-3p. LINC01234 also interacts with the RNA-binding proteins LSD1 and EZH2, leading to histone modification and transcriptional repression of the anti-proliferative genes BTG2. Conclusions: Taken together, our findings identify two oncogenic regulatory axes in NSCLC centering on LINC01234: one involving miR-340-5p/miR-27b-3p in the cytoplasm and the second involving EZH2, LSD1, and BTG2 in the nucleus. Our study indicates that these genes may be targeted to reduce or prevent NSCLC metastasis.

MiRNA-340-5p mediates the functional and infiltrative promotion of tumor-infiltrating CD8+ T lymphocytes in human diffuse large B cell lymphoma

“…Speci cally, an increase in tumor-in ltrating macrophages correlated with poor prognosis in DLBCL patients (38). Furthermore, miR-340-5p was reported to be downregulated and critically involved in tumor suppression in many cancer types (37,(39)(40)(41). Consistent with our results, miR-340-5p regulated DLBCL cell biology and tumor burden in both TME-dependent and TMEindependent manners.…”

MiRNA-340-5p Mediates the Functional and Infiltrative Promotion of Tumor-Infiltrating CD8+ T Lymphocytes in Human Diffuse Large B Cell Lymphoma

“…Speci cally, an increase in tumor-in ltrating macrophages correlated with poor prognosis in DLBCL patients (31). Furthermore, miR-340-5p was reported to be downregulated and critically involved in tumor suppression in many cancer types (30,(32)(33)(34). Consistent with our results, miR-340-5p regulated DLBCL cell biology and tumor burden in both TME-dependent and -independent manners.…”

<p>LncRNA GAS8-AS1 Inhibits Ovarian Cancer Progression Through Activating Beclin1-Mediated Autophagy</p>

“…Western blotting assay was performed as previously described. 26 Briefly, 60 μg protein extractions were loaded via SDS-PAGE and transferred onto nitrocellulose membranes (absin, China); then, incubated with primary antibodies for 2 hrs at temperature, then plated at 4°C overnight, the membranes were incubated in 5% non-fat milk blocking buffer for horizontal mode 3 h. After incubation with secondary antibodies (Lincoln, Nebraska, USA), the membranes were scanned using an Odyssey, and data were analyzed with Odyssey software (LI-COR, USA). Primary antibody lists: LC3 I/II (L7543, Sigma), Beclin1 (ab210498, Abcam), GADPH (ab8245, Abcam).…”