BACKGROUND: Pseudogene-derived long non-coding RNAs (lncRNAs) have been reported to act as key regulatory factors of cancers. However, the study focused on pseudogene misato family member 2 (MSTO2P) in the occurrence and development of colorectal cancer (CRC) remains unclear.
METHODS: CCK-8, colony formation, and transwell assays clarified HT-29 and SW480 cell proliferation and invasion. Furthermore, flow cytometry was carried out to detect cell cycle and cell apoptosis. Subcellular localization assay indicated the location of MSTO2P in HT-29 cells. RIP and CHIP assays clarified the relationship of MSTO2P with target protein and gene in HT-29 cells.
RESULTS: MSTO2P expression was upregulated in CRC tissues and cells. Functional experiments revealed that inhibition of MSTO2P suppressed HT-29 and SW480 cell proliferation and invasion, and promoted cell cycle arrest and cell apoptosis. Besides, MSTO2P epigenetically down-regulated cyclin-dependent kinase inhibitor 1A (CDKN1A) via binding to the enhancer of zeste homolog 2 (EZH2) in the nucleus. At last, rescue experiments proved the anti-tumor effect of inhibition of MSTO2P was partially recovered due to the knockdown of CDKN1A in HT-29 cells.
CONCLUSIONS: LncRNA MSTO2P promoted colorectal cancer progression through epigenetically silencing CDKN1A mediated by EZH2.

Hypoxia has been shown to be related to osteosarcoma development and progression. Pseudogene MSTO2P was reported to be dysregulated in hepatocellular carcinoma and lung cancer. However, the mechanism by which MSTO2P-modulated osteosarcoma remains unclear. MSTO2P and PD-L1 expression levels were examined by RT-qPCR and westernblot. Tumor cell invasion was determined by tranwell assay. EMT process was probed by determining E-cadherin and Vimentin levels. Soft agar assay was used to examine anchorage-independent growth of osteosarcoma cells. In vivo tumor growth was measured by xenografting tumor experiment. Hypoxia treatment promoted cell growth, invasion and EMT of osteosarcoma cells. MSTO2P knockdown led to attenuated cell growth, invasion and EMT of osteosarcoma cells under hypoxia condition. More interestingly, our data revealed that MSTO2P was positively associated with tumor growth in immunodeficient mice and human clinical tissues. PD-L1 was shown to act as a key effector for MSTO2P-regulated osteosarcoma progression under hypoxia condition. In conclusion, we unravel a novel mechanism for explaining MSTO2P-involved osteosarcoma progression under hypoxia condition, which will facilitate development of potential diagnostic and therapeutical strategies for osteosarcoma.

BACKGROUND: Accumulating studies have shown that pseudogenes could become key regulators in human cancers. Misato family member 2, pseudogene (MSTO2P) is overexpressed in lung and gastric cancer and affects the biological functions of tumor cells. However, the role of MSTO2P in hepatocellular carcinoma (HCC) is unreported.
OBJECTIVE: This study aimed to examine the diagnostic and prognostic value of MSTO2P in HCC, to investigate the effects of MSTO2P on the biological functions of HCC cells, and to explore the potential mechanisms of MSTO2P in HCC.
METHODS: Relevant data on HCC were downloaded from the Gene Expression Omnibus database and the Cancer Genome Atlas database and used to analyze MSTO2P expression and the role of MSTO2P in HCC prognosis. MSTO2P in HCC cell lines was knocked down by shRNA to study the effects of MSTO2P on cell proliferation, apoptosis, metastasis and invasion in HCC. Expressions of the main proteins involved in epithelial-mesenchymal transition and the PI3K/AKT/mTOR signaling pathway in HCC were examined via Western blot analysis.
RESULTS: MSTO2P had significant diagnostic and prognostic value in HCC. MSTO2P was highly expressed in HCC tissues and cells, and MSTO2P increased HCC cell proliferation, invasion and metastasis. MSTO2P knockdown also increased E-cadherin expression and decreased N-cadherin and Vimentin expression. Additionally, MSTO2P increased the expressions of proteins in the PI3K/AKT/mTOR pathway, including PI3K, p-AKT and p-mTOR.
CONCLUSIONS: MSTO2P might be used as a potential target for diagnosing and curing HCC. MSTO2P may affect HCC cell proliferation, apoptosis, metastasis and invasion through the PI3K/AKT/mTOR pathway.

Long non-coding RNAs are emerging as new players in gene regulation, but whether long non-coding RNAs influence the expression of microRNA is unclear. The expression levels of misato family member 2, pseudogene were significantly associated with lymphatic metastasis and distal metastasis in 80 paired gastric cancer tissues using real-time quantitative reverse transcription polymerase chain reaction experiments. The effects of long non-coding RNA misato family member 2, pseudogene were assessed by overexpressing or downexpressing long non-coding RNA misato family member 2, pseudogene in gastric cancer cells. Long non-coding RNA misato family member 2, pseudogene promoted gastric cancer cell growth, colony formation, migration, and invasion in gastric cancer cells. Long non-coding RNA misato family member 2, pseudogene influenced biologic functions in gastric cancer cells via indirectly regulating the activation of miR-335. Our results reveal long non-coding RNA misato family member 2, pseudogene as an oncogenic long non-coding RNA that promotes cell growth and invasion. Therefore, long non-coding RNAs might function as key regulatory hubs in gastric cancer progression.