PMID- 37372460 OWN - NLM STAT- MEDLINE DCOM- 20230629 LR - 20230701 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 14 IP - 6 DP - 2023 Jun 16 TI - A Comprehensive Pan-Cancer Analysis of the Potential Biological Functions and Prognosis Values of RICTOR. LID - 10.3390/genes14061280 [doi] LID - 1280 AB - The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been recognized for many years. However, the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway has only recently come to light. The function of RICTOR in pan-cancer still needs to be systematically elucidated. In this study, we examined RICTOR's molecular characteristics and clinical prognostic value by pan-cancer analysis. Our findings indicate that RICTOR was overexpressed in twelve cancer types, and a high RICTOR expression was linked to poor overall survival. Moreover, the CRISPR Achilles' knockout analysis revealed that RICTOR was a critical gene for the survival of many tumor cells. Function analysis revealed that RICTOR-related genes were mainly involved in TOR signaling and cell growth. We further demonstrated that the RICTOR expression was significantly influenced by genetic alteration and DNA-methylation in multiple cancer types. Additionally, we found a positive relationship between RICTOR expression and the immune infiltration of macrophages and cancer-associated fibroblasts in Colon adenocarcinoma and Head and Neck squamous cell carcinoma. Finally, we validated the ability of RICTOR in sustaining tumor growth and invasion in the Hela cell line using cell-cycle analysis, the cell proliferation assay, and wound-healing assay. Our pan-cancer analysis highlights the critical role of RICTOR in tumor progression and its potential as a prognostic marker for various cancer types. FAU - Sun, Ying AU - Sun Y AD - Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. FAU - Li, Rui AU - Li R AD - MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. FAU - Nong, Baoting AU - Nong B AD - Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. FAU - Songyang, Zhou AU - Songyang Z AD - MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. FAU - Wang, Xianren AU - Wang X AD - Department of Otolarygology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. FAU - Ma, Wenbin AU - Ma W AUID- ORCID: 0000-0001-8774-7593 AD - MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. FAU - Zhou, Qin AU - Zhou Q AUID- ORCID: 0000-0002-7205-082X AD - Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - NHC Key Laboratory of Clinical Nephrology and Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou 510080, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230616 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (Rapamycin-Insensitive Companion of mTOR Protein) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 0 (Transcription Factors) RN - W36ZG6FT64 (Sirolimus) RN - 0 (RICTOR protein, human) SB - IM MH - Humans MH - HeLa Cells MH - *Adenocarcinoma MH - Rapamycin-Insensitive Companion of mTOR Protein/genetics/metabolism MH - *Colonic Neoplasms MH - TOR Serine-Threonine Kinases/genetics/metabolism MH - Transcription Factors/metabolism MH - Sirolimus MH - Prognosis PMC - PMC10298440 OTO - NOTNLM OT - Pan-cancer OT - RICTOR OT - mTORC2 COIS- The authors declare no conflict of interest. EDAT- 2023/06/28 06:42 MHDA- 2023/06/29 06:42 PMCR- 2023/06/16 CRDT- 2023/06/28 01:13 PHST- 2023/05/06 00:00 [received] PHST- 2023/06/01 00:00 [revised] PHST- 2023/06/14 00:00 [accepted] PHST- 2023/06/29 06:42 [medline] PHST- 2023/06/28 06:42 [pubmed] PHST- 2023/06/28 01:13 [entrez] PHST- 2023/06/16 00:00 [pmc-release] AID - genes14061280 [pii] AID - genes-14-01280 [pii] AID - 10.3390/genes14061280 [doi] PST - epublish SO - Genes (Basel). 2023 Jun 16;14(6):1280. doi: 10.3390/genes14061280.