lncRNA HCG11 Promotes Colorectal Cancer Cell Malignant Behaviors via Sponging miR-26b-5p.

Colorectal cancer (CRC) is a type of gastrointestinal cancer with an increasing incidence. Long noncoding RNAs (lncRNAs) have raised great concern because of wide participation in human diseases, including cancers. However, whether lncRNA HLA complex group 11 (HCG11) played a functional role in CRC remained to be elucidated. Herein, we utilized qRT-PCR to analyze the expression of HCG11 and found that HCG11 was highly expressed in CRC cells. Besides, HCG11 knockdown suppressed cell proliferation, migration, and invasion but facilitated cell apoptosis. Furthermore, supported by bioinformatics analyses and mechanism assays, HCG11, mainly located in cell cytoplasm, was confirmed to competitively bind to miR-26b-5p to modulate the expression of the target messenger RNA (mRNA), namely, cAMP-regulated phosphoprotein 19 (ARPP19). ARPP19 was detected to be upregulated in CRC cells, and ARPP19 silence was verified to inhibit the malignant behaviors of CRC cells. Rescue experiments validated that miR-26b-5p inhibition or ARPP19 overexpression could countervail the inhibitory influences of HCG11 silence on CRC cell biological behaviors in vitro. To conclude, HCG11, upregulated in CRC cells, could promote cell proliferation, migration, and invasion and inhibit cell apoptosis via targeting miR-26b-5p/ARPP19 axis.

LINC00882 Plays a Tumor-promoter Role in Colorectal Cancer by Targeting miR-3619-5p to Up-regulate CTNNB1.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract around the world. Emerging evidence has confirmed that long non-coding RNAs (lncRNAs) are closely connected to cell progression in cancers, including CRC. METHODS: RT-qPCR assays were applied to detect the expression of LINC00882, miR-3619-5p and CTNNB1. Western blot assays were performed to measure the protein level of E-cadherin, N-cadherin and CTNNB1. Transwell assay was conducted to test the cell migration. Immunofluorescence (IF) assay was performed to measure the connected protein of EMT process. RESULTS: LINC00882 was highly expressed in CRC tissues and cell lines. Knockdown of LINC00882 hindered the process of CRC. Studies on gain-of-function and loss-of-function further testified that knockdown of LINC00882 or up-regulation of miR-3619-5p hindered cell migration and EMT process in CRC cells. Moreover, rescue assay proved that the inhibition of migration ability and EMT process resulted from LINC00882 silencing could be rescued when miR-3619-5p inhibitor or pcDNA3.1/CTNNB1 was transfected into CRC cells. CONCLUSION: Our data suggested that LINC00882 promoted the progression of CRC as a ceRNA to regulate CTNNB1 via sponging miR-3619-5p. This finding would supply a novel insight for CRC therapy.

Long non-coding RNA AGAP2-AS1 accelerates cell proliferation, migration, invasion and the EMT process in colorectal cancer via regulating the miR-4,668-3p/SRSF1 axis.

BACKGROUND: Colorectal cancer (CRC) is a frequently occurring tumor. Although a number of long noncoding RNAs have been researched in CRC, the expression, function and mechanism of AGAP2-AS1 remains poorly investigated. METHODS: Gene expression was analyzed by a quantitative reverse transcriptase-polymerase chain rreaction and western blot analyses. Cell counting kit-8, colony formation and Transwell assays were utilized to explore the functional role of AGAP2-AS1 in CRC. Luciferase reporter, RNA pull down and RNA immunoprecipitation assays were implemented to verify relationships between RNA molecules. RESULTS: In the present study, AGAP2-AS1 was unveiled as highly expressed in CRC cell lines compared to normal cells. AGAP2-AS1 knockdown suppressed cell proliferation, migration, invasion and the epithelial-to-mesenchymal transition process. Interestingly, AGAP2-AS1 sponges miR-4,668-3p to release SRSF1 in CRC. Furthermore, in the rescue functional assay, miR-4,668-3p down-regulation exacerbated the malignant behaviors of AGAP2-AS1-depleted CRC cells, whereas such effects were further offset by SRSF1 knockdown. CONCLUSIONS: AGAP2-AS1 facilitates cell proliferation, motility and EMT in CRC via targeting the miR-4,668-3p/SRSF1 axis. AGAP2-AS1 or SRSF1 may have potential as underlying therapeutic targets for CRC patients.

TGF-ß induces HLA-G expression through inhibiting miR-152 in gastric cancer cells.

BACKGROUND: Mounting evidences have showed the important role of transforming growth factor-ß (TGF-ß) in immunological surveillance of tumors. Some studies have also indicated human leukocyte antigen (HLA)-G-associated immune escape involving TGF-ß management in gastric cancer (GC). However, the mechanism underlying it is unclear. This study aims to verify the correlations between HLA-G and TGF-ß, involving the potential targeting of miR-152 on HLA-G. RESULTS: TGF-ß and HLA-G levels were analyzed in blood samples from twenty GC patients with ELISA assays, while TGF-ß showed directly proportional to HLA-G levels in GC patients, and TGF-ß induced HLA-G up-regulation was also confirmed in GC cell lines. Furthermore, miR-152 expression could be inhibited by TGF-ß, and the negative post-transcriptionally regulation of miR-152 on HLA-G was also demonstrated through gain- and loss-of-function studies. Besides, miR-152 overexpression repressed HLA-G up-regulation induced by TGF-ß. And, miR-152 expression levels showed inversely proportional to both HLA-G and also TGF-ß levels in GC patients. CONCLUSION: TGF-ß could induce HLA-G expression in GC by inhibiting miR-152, involving its negative regulation on HLA-G. Since TGF-ß induced HLA-G up-regulation plays important role in immune escape, a potential application of miR-152 was suggested in GC treatment, or miR-152 might be one potential biomarker for GC.

Long non-coding RNA HOTAIR promotes HLA-G expression via inhibiting miR-152 in gastric cancer cells.

Recent studies have shown that the long non-coding RNA HOTAIR plays critical roles in tumor biology, including cancer progression and metastasis. However, the potential biological role HOTAIR in tumor escape remains undefined. Here, HOTAIR expression was measured in sixty paired gastric cancer (GC) tissue samples by real-time PCR, and then subjected to correlation analysis with human leukocyte antigen (HLA)-G levels which show close links with tumor escape mechanisms. Significant HOTAIR overexpression was observed in GC tissues, as well as strong positive correlations with HLA-G levels in both tissue and peripheral blood samples, detected by real-time PCR and ELISA assays respectively. Further gain- and loss-of-function studies indicated that HLA-G could be upregulated HOTAIR at both mRNA and secretion levels in vitro. On the other hand, bioinformatics analysis indicated the interaction between HOTAIR and miR-152, which shows potential regulation on HLA-G. And, altered miR-152 expression in GC tissues was also identified, and showed negative correlation with HOTAIR expression. Moreover, the negative regulation of miR-152 on HLA-G was verified in GC cells, while miR-152 induced decrease of HLA-G 3'UTR activity could be attenuated by HOTAIR co-overexpression with the assistant of mutation studies. Therefore, it was concluded that HOTAIR overexpression might also get involved in tumor escape mechanisms, involving HLA-G upregulation via inhibiting miR-152. Furthermore, this study recommended the potential application of HOTAIR in GC immunotherapy for better prognosis and improved survival.