LncRNA RPLP0P2 Promotes Colorectal Cancer Proliferation and Invasion via the miR-129-5p/Zinc Finger and BTB Domain-Containing 20 Axis.

We previously reported that long non-coding RNA (lncRNA) RPLP0P2 is involved in the progression of colorectal cancer (CRC); however, its molecular mechanisms in CRC remain unclear. In this study, we observed that RPLP0P2 was upregulated in CRC tissues and cell lines. Cell viability was measured using the MTT and colony formation assays. Migration and invasion capabilities were monitored by wound healing, transwell, and immunofluorescence assays. The results showed that RPLP0P2 downregulation inhibited cell viability, migration, and invasion capabilities of CRC cells, accompanied by decreased PCNA, N-cadherin, and Vimentin, and increased E-cadherin expression. Using the DIANA online database, miR-129-5p was identified as a downstream target of RPLP0P2. In fact, RPLP0P2 colocalized with miR-129-5p, acting as a miR-129-5p sponge. MiR-129-5p-inhibition almost abrogated the anti-tumor effects induced by RPLP0P2 inhibition in CRC cells. Zinc finger and BTB domain-containing 20 (ZBTB20) was identified as a potential downstream target of miR-129-5p in CRC cells. ZBTB20 overexpression prevented miR-129-5p mimic-mediated anti-tumor effects in CRC cells. A tumor xenograft assay was performed to monitor the role of RPLP0P2 in tumor growth. Of note, in tumor-bearing mice, RPLP0P2-silencing inhibited tumor growth, followed by increased miR-129-5p and decreased ZBTB20 expression. Our results suggest that lncRNA RPLP0P2 functions as an oncogene that promotes CRC cell proliferation and invasion via regulating the miR-129-5p/ZBTB20 axis, thus, it may serve as a candidate target for CRC interventional therapies.

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway.

Objective: BHLHE41 has been shown to be a marker of tumorigenesis. Colon cancer (CC) is a common malignant tumor of colonic mucosa. This study mainly explored the mechanism of BHLHE41 in alleviating malignant behavior of hypoxia-induced CC cells. Methods: The levels of BHLHE41 in CC and normal cell lines were tested by Western blot and qRT-PCR. After, CC cells were subjected to hypoxia treatment and BHLHE41 overexpression transfection, and the BHLHE41 expression, the effect of BHLHE41 on CC cell viability, apoptosis, migration, and invasion and cell cycle were tested by qRT-PCR and relevant cell functional experiments. HIF-1α and epithelial-mesenchymal transition- (EMT-) related proteins were tested by Western blot. Moreover, CC tumor-bearing model was established in nude mice, and the effect of BHLHE41 on the tumor was evaluated by measuring the tumor volume and weight. Then, the expressions of BHLHE41 and EMT-related proteins were detected by immunohistochemistry and Western blot. Results: Western blot and qRT-PCR showed that BHLHE41 was lowly expressed in CC cells. BHLHE41 overexpression could inhibit the hypoxia-induced CC cell viability, migration, and invasion, induce apoptosis, and alter cell cycle. Besides, BHLHE41 overexpression could enhance the levels of E-cadherin but reduce the levels of HIF-1α, N-cadherin, vimentin, and MMP9 in hypoxia-induced CC cells. Moreover, BHLHE41 overexpression reduced tumor volume, weight, and EMT-related proteins levels in tumor tissues. Conclusions: BHLHE41 overexpression could mitigate the malignant behavior of hypoxia-induced CC via modulating the HIF-1α/EMT pathway.

WITHDRAWN: LncRNA USP1 Knockdown Weakens the Progression of Colorectal Cancer via Modulating UBAP2L-Smad7-TGF-ß Pathway

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Schizandrin A exhibits potent anticancer activity in colorectal cancer cells by inhibiting heat shock factor 1.

Heat shock factor 1 (HSF1) is a powerful multifaceted oncogenic modifier that plays a role in maintaining the protein balance of cancer cells under various stresses. In recent studies, there have been reports of increased expression of HSF1 in colorectal cancer (CRC) cells, and the depletion of the HSF1 gene knockdown has inhibited colon cancer growth both in vivo and in vitro. Therefore, HSF1 is a promising target for colon cancer treatment and chemoprevention. In the present study, we found that Schizandrin A (Sch A) significantly inhibited the growth of CRC cell lines by inducing cell cycle arrest, apoptosis and death. Through HSE luciferase reporter assay and quantitative PCR (qPCR), we identified Sch A as a novel HSF1 inhibitor. In addition, Sch A could effectively inhibit the induction of HSF1 target proteins such as heat-shock protein (HSP) 70 (HSP70) and HSP27, whether in heat shock or normal temperature culture. In the Surface Plasmon Resonance (SPR) experiment, Sch A showed moderate affinity with HSF1, further confirming that Sch A might be a direct HSF1 inhibitor. The molecular docking and molecular dynamic simulation results of HSF1/Sch A suggested that Sch A formed key hydrogen bond and hydrophobic interactions with HSF1, which may contribute to its potent HSF1 inhibition. These findings provide clues for the design of novel HSF1 inhibitors and drug candidates for colon cancer treatment.

Morphology Parameters for Mirror Posterior Communicating Artery Aneurysm Rupture Risk Assessment.

Recent studies have shown that posterior communicating artery (PComA) aneurysms are more likely to rupture. However, surgical intervention for PComA aneurysms may be associated with increased treatment-related morbidity rate. Therefore, it is meaningful to investigate the factors related to PComA aneurysm rupture. The purpose of this study was to identify morphological parameters that significantly correlate with PComA aneurysm rupture. We divided 14 pairs of mirror posterior communicating artery aneurysms (PComA-MANs) into ruptured and unruptured groups. Computed tomography angiography (CTA) imaging was evaluated with three-dimensional (3D) Slicer to generate models of the aneurysms and surrounding vasculature. Nine morphological parameters [size, height, width, neck width, aspect ratio (AR), bottleneck factor (BNF), height/width ratio (H/W), size ratio (SR), and bleb formation] were examined in the two groups for significance with respect to rupture. By contrast, statistically significant differences were found in ruptured and unruptured group for size, AR, BNF, SR, and bleb formation (P < 0.05). Parameters that had no significant differences between the two groups were height (P = 0.103), width (P = 0.078), neck width (P = 0.808), and H/W (P = 0.417). We conclude that MANs may be a useful model for the morphological analysis of intracranial aneurysm rupture. Larger size, higher AR, BNF, SR, and bleb formation may be related to rupture of PComA aneurysms. Larger sample studies minimizing the interference from patient-related factors and aneurysm type were expected for acquiring more accurate assessment of the relationship between these parameters and PComA aneurysm rupture.