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Introduction. The purpose of this study is to elucidate the impact of long non-coding RNA (lncRNA) MIR4435- 2HG/microRNA (miR)-125b-5p/ Semaphorins 4D (Sema4D) on colorectal cancer (CRC) cell propagation and migration. Material and methods. Sema4D expression in 73 pairs of CRC tissues and matched adjacent normal tissues was measured by qRT-PCR and western blot and its association with pathological characteristics of CRC patients was analyzed by chi-square test. Also, the expression of MIR4435-2HG, miR-125b-5p and Sema4D in CRC cell lines was detected by qRT-PCR and Western blot. Knockdown or overexpression of MIR4435-2HG, miR-125b5p and Sema4D were separately performed in Caco-2 and LoVo cells, and the cell propagation, migration and invasiveness were detected by cell-counting kit 8, scratch, and transwell assays. Results. LncRNA MIR4435-2HG and Sema4D were highly expressed, while miR-125b-5p expression was decreased in CRC tissues and cells. Knockdown of MIR4435-2HG/Sema4D or overexpression of miR-125b-5p inhibited CRC cell proliferation and aggressiveness; overexpression of MIR4435-2HG/Sema4D or knockdown of miR-125b-5p prompted the malignant behaviors of cancer cells. MIR4435-2HG and Sema4D competitively bound to miR-125b-5p. Conclusions. LncRNA MIR4435-2HG targets miR-125b-5p to upregulate Sema4D expression, and thus regulates CRC cell propagation, migration and invasiveness. [ABSTRACT FROM AUTHOR]

Background: In the current study, we used the information-hierarchical system approach to examine human metabolism. Metabolism hierarchical structure, beginning from enzyme level, is controlled by the established information principle and divine section numbers. This structure represents a key mechanism of the hierarchical biological clock (HBC) of human body. Time cycles of HBC hierarchical levels are nested into each other according to strict dynamics schemes. The cycles form the HBC scales of 1, 6, 42 seconds, 24 hours (circadian rhythm), and 11 days and jointly make up the precision HBC similar to the conventional countdown (1 s, 1 m, 1 hr, 1 day, and 1 month). Method: Diagnostic/prognostic studies of cancer require a detailed analysis of metabolic HBC disorders. We utilized the information-hierarchical system approach and the information principle in order to analyze HBC run under different dietary patterns. Results: We characterized hierarchical metabolic systems with 24-hour and 11- day operation times. The 24-hour circadian rhythm comprised citrate, pentose, and fatty acid (anabolic or catabolic) biochemical cycles individually. The 11-day cyclicity referred to these cycles combined into a ternary system of the higher-rank hierarchical level. Disorder of systems operation should lead to a radical change in HBC run with subsequent transformation of normal cells into cancer cells. Conclusion: Mutations of metabolic enzyme genes can damage HBC run, thereby leading to cancer and other chronobiological disorders. Organized rhythmicity of external factors (everyday food intake, 11-day periodical dietary pattern, and so forth) made it possible to heal cancer cells per se. Applying a particular kind of diet, the human lifespan could significantly increase. The proposed direction of cancer prevention and treatment can be called a cancer metabolism chronotherapy. [ABSTRACT FROM AUTHOR]