LncRNA MALAT1 modified progression of clear cell kidney carcinoma (KIRC) by regulation of miR-194-5p/ACVR2B signaling.
This investigation was purposed to extrapolate whether and how lncRNA MALAT1, miR-194-5p, and ACVR2B altered development of clear cell kidney carcinoma (KIRC). We totally gathered 318 pairs of KIRC tissues and adjacent normal tissues, and also purchased human KIRC cell lines and normal human proximal tubular epithelial cell line. Besides, si-MALAT1, pcDNA-MALAT1, miR-194-5p mimic, miR-194-5p inhibitor, and negative control (NC) were, respectively, transfected into KIRC cells. The viability, proliferation, and apoptosis of the cells were determined with CCK-8 assay, colony formation assay, and flow cytometry. Dual-luciferase reporter gene assay was implemented to validate the targeted relationships between MALAT1 and miR-194-5p, as well as between miR-194-5p and ACVR2B. The results showed that highly expressed MALAT1, ACVR2B, and lowly expressed miR-194-5p were associated with larger tumor size (≥4 cm), advanced TNM stage and poor prognosis of KIRC patients, when, respectively, compared with lowly expressed MALAT1, ACVR2B, and highly expressed miR-194-5p (P < 0.05). Transfection of pcDNA-MALAT1, miR-194-5p inhibitor, and pcDNA-ACVR2B conferred the KIRC cells with promoted viability and proliferation, as well as reduced apoptosis (P < 0.05). Treatment of rats with pcDNA-MALAT1, miR-194-5p inhibitor, or pcDNA-ACVR2B also contributed to larger tumor size growing in them (P < 0.05). Moreover, MALAT1 could directly target miR-194-5p to suppress its expression, and ACVR2B was the targeted molecule of miR-194-5p (P < 0.05). Finally, ACVR2B could reverse the effects exerted by miR-194-5p on viability, proliferation, and apoptosis of KIRC cells (P < 0.05). In conclusion, LncRNA MALAT1/miR-194-5p/ACVR2B signaling was regarded as a candidate pathway for modulating KIRC progression.
Ye Y
，Zhang F
，Chen Q
，Huang Z
，Li M
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Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 regulates the expression of Gli2 by miR-202 to strengthen gastric cancer progression.
Gastric cancer (GC) is one of the most common malignancies and ranks the second leading cause of cancer death worldwide. Some studies had reported the tumor-promoting effects of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a competing endogenous RNA (ceRNA) by sponging to microRNAs. However, the molecular mechanism of ceRNA regulatory pathway involving MALAT1 in GC remains unclear.
MALAT1 and miR -202 expression was detected by quantitative real time PCR (qRT-PCR) in 60 gastric cancer tissues and adjacent normal tissues, CCK8 cell proliferation assays, cell cycle analysis and cell apoptosis assays were performed to detect the GC cell proliferation and apoptosis. The mRNA and protein levels of Gli2 were analyzed by quantitative real-time PCR and Western blotting assays. Furthermore, using online software, luciferase reporter assays, RNA immunoprecipitation (RIP) and RNA pulldown assays demonstrated miR-202 was a target of MALAT1.
We found that MALAT1 was upregulated in GC tissues and higher MALAT1 expression was correlated with larger tumor size, lymph node metastasis, and TNM stage. Moreover, we revealed that MALAT1 was a direct target of miR-202 and knockdown of MALAT1 significantly decreased the expression of Gli2 through negatively regulating miR-202. In addition, knockdown of Malat1 inhibited GC cells proliferation, S-phase cell number, and induced cell apoptosis via negatively regulating miR-202 in vitro.
Our results elucidated MALAT1/miR-202/Gli2 regulatory pathway, which maybe contribute to a novel therapeutic strategy for GC patients.
Zhang Y
，Chen Z
，Li MJ
，Guo HY
，Jing NC
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ResearchGate
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