MicroRNAs　(miRNAs)　play　an　important　role　in　the　regulation　of　various　biological　processes　and　have　been　used　as　potential　biomarkers　for　biomedical　research　and　clinical　diagnosis.　Here,　nicking-mediated　rolling　circle　amplification　(N-RCA)/symmetric　isothermal　circular　strand-displacement　amplification　(S-SDA)-integrated　combined　cascade　amplification　(rs-CCA)　was　proposed　for　let-7a　miRNA　detection.　Via　introducing　a　palindromic　fragment-integrated　recognition　sites　for　nicking　endonuclease　Nt.AlWI　into　the　padlock　probe,　the　hybridization　of　target　miRNA　can　induce　N-RCA　and　continuously　generate　the　nicked　fragments　(NFs).　Because　the　released　NFs　each　have　a　palindromic　sequence　and　daughter　nicking　site　at　the　3’　end,　they　hybridize　with　each　other,　followed　by　alternately　extension　by　polymerase　and　nicking　by　endonuclease.　This　leads　to　S-SDA　effect,　and　the　released　single-stranded　products　in　turn　hybridize　with　NFs,　accomplishing　the　rs-CCA　process.　When　the　Sybr　Green　I　dyes　intercalate　into　double-stranded　DNA　products,　the　amplified　fluorescence　signal　is　achieved.　Thus,　the　target　miRNA　can　be　detected　down　to　5　pM.　Importantly,　the　rs-CCA　system　is　capable　of　distinguishing　the　single　base　difference　between　target　miRNAs,　indicating　the　high　sequence　specificity.　Moreover,　its　potential　application　in　disease　diagnosis　was　demonstrated　via　detecting　target　miRNA　in　complex　biological　matrix　and　analyzing　the　total　RNAs　extracted　from　HeLa　cells.　As　a　proof-of-concept　building,　the　impressive　rs-CCA　scheme　is　expected　to　provide　a　valuable　insight　into　constructing　powerful　signal　amplification　strategies　via　sophisticated　combination　of　biotechnologies　available　for　nucleic　acid　manipulation　and　significantly　benefit　biomedical　research　and　disease　diagnostics.　©　2018　Elsevier　B.V.