LncRNA PART1 facilitates the malignant progression of colorectal cancer via miR-150-5p/LRG1 axis.

Study has shown that long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was elevated in colorectal cancer tissues and cells, and the proliferation and metastasis of colorectal cancer cells were reduced after its downregulation. The tumor-suppressive role of microRNA-150-5p (miR-150-5p) has been shown in colorectal cancer. In this study, the association between PART1 and miR-150-5p in colorectal cancer was analyzed. Results revealed an increase of PART1, but a decrease of miR-150-5p in 56 colorectal cancer tissues. And there was a strong negative correlation between levels of PART1 and miR-150-5p in these cancer samples. Also, compared with 10 healthy controls, the level of PART1 was increased, whereas miR-150-5p expression was diminished in the serum of 10 colorectal cancer patients. Cell proliferation and migration, along with epithelial-mesenchymal transition, was promoted by PART1 overexpression. However, this lncRNA mitigated apoptosis of colorectal cancer cells. Whereas miR-150-5p mimic abrogated these effects caused by PART1 overexpression. The influences of PART1 knockdown on the above malignant characteristics of colorectal cancer cells were contrary to its overexpression. miR-150-5p inhibitor ablated the effects induced by PART1 knockdown. In xenograft mouse models, silencing of PART1 decreased tumor volume and weight. Our data supported that lncRNA PART1 may regulate leucine-rich α-2-glycoprotein-1 (LRG1) expression through a competing interaction mechanism that hindering miR-150-5p function. In conclusion, PART1 facilitates the malignant progression of colorectal cancer via miR-150-5p/LRG1 pathway. The study further clarified the molecular mechanism of PART1 in colorectal cancer. This study may provide a new approach to diagnose and treat colorectal cancer.

Lou T ，Ke K ，Zhang L ，Miao C ，Liu Y ... -  《-》

Long noncoding RNA PRKCQ-AS1 promotes CRC cell proliferation and migration via modulating miR-1287-5p/YBX1 axis.

Colorectal cancer (CRC) brings more than 600 000 deaths every year around the globe, making itself the third most frequently occurred carcinoma. The great progress human achieved in diagnosis and treatment of various cancers has failed to reverse this trend. Fortunately, growing evidence has implied the relationship between lncRNAs and cancer progression. Long noncoding RNA (lncRNA) PRKCQ-AS1 was heightened in CRC cells and tissues and related with dismal prognosis of CRC patients. Knockdown of PRKCQ-AS1 would induce a decrease in proliferative and migrating ability of CRC cells. Also, PRKCQ-AS1 enriched in cytoplasm of CRC cells and negatively regulated miR-1287-5p level. More important, PRKCQ-AS1 could bind to argonaute 2 and function in the RNA-induced silencing complex with miR-1287-5p. Therefore, PRKCQ-AS1 was a competing endogenous RNA for miR-1287-5p. Subsequently, it was validated that miR-1287-5p could suppress the proliferative and migratory functions in CRC. Furthermore, PRKCQ-AS1 could upregulate the mRNA and protein level of YBX1 targeted by miR-1287-5p. And YBX1 expression was elevated in CRC cells and tissues. Rescue assays in vitro and in vivo showed that overexpression of YBX1 could partly offset the effect of CRC progression induced by knocking down PRKCQ-AS1, demonstrating PRKCQ-AS1 mediating CRC progression via miR-1287-5p/YBX1 pathway.

Cui G ，Zhao H ，Li L 《-》

Repression of lncRNA PART1 attenuates ovarian cancer cell viability, migration and invasion through the miR-503-5p/FOXK1 axis.

Ovarian cancer (OC) is a female malignant tumor with a high fatality rate. Long non-coding RNAs (lncRNAs) are deeply involved in OC progression. The aim of this study is to explore the specific mechanism of lncRNA prostate androgen-regulated transcript 1 (PART1) in OC. Quantitative real time PCR was utilized to determine the expression levels of PART1, microRNA (miR)-503-5p and forkhead-box k1 (FOXK1) in OC tissues and/or cells. The cell viability, migration, and invasion in OC were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, wound healing assay and transwell invasion assay, respectively. Flow cytometry was used to analyze the cell apoptosis. The xenograft tumor was conducted in nude mice to verify the effect of PART1 knockdown on OC in vivo. The target relationships among PART1, miR-503-5p and FOXK1 were predicted by StarBase, and verified by luciferase reporter assay. The level of FOXK1 was assessed by western blot. Increased expression of PART1 and FOXK1 was observed in OC tissues or cells, whereas miR-503-5p was downregulated. PART1 silencing or miR-503-5p overexpression repressed the cell viability, migration and invasion, and protomed apoptosis. Meanwhile, miR-503-5p was a target of PART1, and FOXK1 was a direct target gene of miR-503-5p. Both downregulation of miR-503-5p and upregulation of FOXK1 partly relieved the suppressive effects of PART1 knockdown on the oncogenicity of OC in vitro. Decreased PART1 represses the cell viability, migration and invasion of OC via regulating the miR-503-5p/FOXK1 axis, which provided an underlying target for treating OC.

Li B ，Lou G ，Zhang J ，Cao N ，Yu X ... -  《BMC CANCER》

Long noncoding RNA LINC01234 promoted cell proliferation and invasion via miR-1284/TRAF6 axis in colorectal cancer.

Colorectal cancer is one of the most common and leading malignancies globally. Long noncoding RNAs (lncRNAs) function as potentially critical regulator in colorectal cancer. LINC01234, a novel lncRNA in tumor biology, regulates the progression of various tumors. However, the tumorigenic mechanism of LINC01234 in colorectal cancer is still unclear. This study was performed with the aim to prospectively investigate clinical significance, effect, and mechanism of lncRNA LINC01234 in colorectal cancer. First, we found that LINC01234, localized in the cytoplasm, was increased in both colorectal cancer cell lines and tissues. Subsequent functional assays suggested LINC01234 knockdown suppressed cell proliferation, migration, and invasion of colorectal cancer cells, while blocked cell cycle and induced cell apoptosis. Moreover, we identified that miR-1284 was target of LINC01234, we further demonstrated a negative correlation with LINC01234 in colorectal cancer tissues and cells. Furthermore, miR-1284 targeted and suppressed tumor necrosis factor receptor-associated factor 6 (TRAF6). Loss-of-function assay revealed that LINC01234 silencing suppressed colorectal cancer progression through inhibition of miR-1284. In vivo subcutaneous xenotransplanted tumor model indicated LINC01234 knockdown inhibited in vivo tumorigenic ability of colorectal cancer via downregulation of TRAF6. Collectively, this study clarified the biological significance of LINC01234/miR-1284/TRAF6 axis in colorectal cancer progression, providing insights into LINC01234 as novel potential therapeutic target for colorectal cancer therapeutic from bench to clinic.

Liao X ，Zhan W ，Zhang J ，Cheng Z ，Li L ，Tian T ，Yu L ，Li R ... -  《-》

LncRNA PART1 regulates colorectal cancer via targeting miR-150-5p/miR-520h/CTNNB1 and activating Wnt/β-catenin pathway.

Numerous studies have reported that lncRNAs could play a significant role in carcinogenesis. PART1, as an identified lncRNA, was an oncogene in several cancers. However, the underling mechanism of PART1 regulating colorectal cancer remains unknown. qRT-PCR was used to measure relevant RNAs expression. CCK8 and colony formation were combined to evaluate cell proliferation. Tunel and flow cytometry were performed to access cell apoptosis. Wound healing and Transwell assay testified cell invasion and migration ability. Relevant protein expression level was measured via Western blot assay. TOP/FOP luciferase assay determined the activity of Wnt/β-catenin pathway. According to experiment findings, PART1 was up-regulated in CRC tissues and cell lines. Inhibition of PART1 hindered CRC cell proliferation, invasion and migration, while promoting CRC cell apoptosis. Experiments in vivo also validated this result. Mechanistically, PART1 sponged miR-150-5p/miR-520 h to up-regulate CTNNB1, thus activating Wnt/β-catenin pathway in CRC. In summary, PART1 could up-regulate CTNNB1 via sponging miR-150-5p/miR-520 h.

Zhou T ，Wu L ，Ma N ，Tang F ，Zong Z ，Chen S ... -  《-》